{"gene":"CTNND1","run_date":"2026-06-09T22:57:19","timeline":{"discoveries":[{"year":1994,"finding":"p120ctn (p120cas) was identified as a new catenin that associates with the E-cadherin complex containing alpha-catenin, beta-catenin, and plakoglobin, and precisely colocalizes with E-cadherin and catenins in vivo; in Src-transformed MDCK cells, p120, beta-catenin, and plakoglobin were heavily phosphorylated on tyrosine, but the physical associations were not disrupted.","method":"Co-immunoprecipitation, immunofluorescence colocalization, immunoblotting in MDCK cells","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — reciprocal Co-IP and colocalization, foundational paper replicated extensively by subsequent work","pmids":["7526156"],"is_preprint":false},{"year":1995,"finding":"p120ctn (CAS) binds directly to E-cadherin via its Arm repeats 1–10, independently of alpha-catenin, and does not interact with APC or alpha-catenin; direct interaction confirmed in yeast two-hybrid system.","method":"Yeast two-hybrid, cell line analysis (PC3, SW480, HCT116)","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — direct binding confirmed by yeast two-hybrid with domain mapping, replicated across multiple cell lines and subsequent studies","pmids":["7651399"],"is_preprint":false},{"year":1996,"finding":"p120ctn associates with N-cadherin and P-cadherin (not only E-cadherin) via its Armadillo repeat domain; overexpression in NIH3T3 cells induces a striking dendrite-like branching morphological phenotype dependent on an intact Arm domain.","method":"Co-immunoprecipitation, transfection of CAS mutants in MDCK and NIH3T3 cells, immunofluorescence","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — Co-IP across multiple cadherin types and domain-deletion mutant analysis, single lab","pmids":["8660921"],"is_preprint":false},{"year":1998,"finding":"The juxtamembrane region of the cadherin cytoplasmic tail is the major binding site for p120ctn and is required for ligand-dependent cadherin clustering and adhesive strengthening; p120ctn was purified as the major protein binding this region.","method":"Affinity purification of proteins binding juxtamembrane region, deletion mutant analysis, laminar flow detachment assays, aggregation assays in Xenopus C-cadherin system","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — biochemical purification combined with functional adhesion assays, multiple orthogonal methods","pmids":["9566976"],"is_preprint":false},{"year":1998,"finding":"The human CTNND1 gene comprises 21 exons and encodes up to 32 protein isoforms via alternative splicing and multiple translation initiation codons; isoforms 1–4 differ by start codon used, with additional variation from alternatively spliced exons A, B, and C.","method":"cDNA cloning, exon mapping, RT-PCR isoform analysis","journal":"Genomics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic molecular cloning and transcript analysis, single lab but comprehensive","pmids":["9653641"],"is_preprint":false},{"year":1999,"finding":"p120ctn interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor, via Arm repeats 1–7 of p120ctn and the C-terminal 200 amino acids of Kaiso; Kaiso localizes to the nucleus and co-precipitates specifically with p120ctn antibodies but not with antibodies to alpha- or beta-catenin, E-cadherin, or APC.","method":"Yeast two-hybrid screen, monoclonal antibody co-immunoprecipitation, immunolocalization in mammalian cells","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 1 / Strong — yeast two-hybrid with domain mapping confirmed by reciprocal Co-IP and immunolocalization","pmids":["10207085"],"is_preprint":false},{"year":1999,"finding":"p120ctn binds the membrane-proximal region of E-cadherin and negatively regulates adhesion activity; amino-terminally deleted p120ctn (lacking serine/threonine phosphorylation sites) activates nonfunctional E-cadherin; staurosporine-induced mobility shift of p120ctn correlates with cadherin activation and converts E-cadherin from cytochalasin D-sensitive to insensitive state.","method":"Deletion construct transfection, co-immunoprecipitation, aggregation assays, kinase inhibitor (staurosporine) treatment","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple functional assays with deletion mutants, single lab","pmids":["10409703"],"is_preprint":false},{"year":1999,"finding":"p120ctn nuclear localization is counteracted by a leucine-rich nuclear export signal (NES) encoded by alternatively spliced exon B; expression of E-cadherin directs p120ctn out of the nucleus; nuclear export of exon-B-containing isoforms is sensitive to leptomycin B; PKC activation increases nuclear p120ctn.","method":"Overexpression of isoforms, microinjection of NES-carrier fusion proteins, leptomycin B treatment, immunofluorescence in multiple carcinoma cell lines","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — NES function validated autonomously by microinjection, multiple orthogonal methods in one study","pmids":["10393933"],"is_preprint":false},{"year":2000,"finding":"Selective uncoupling of p120ctn from E-cadherin (via minimal juxtamembrane domain mutations) disrupts E-cadherin-mediated strong adhesion; p120ctn is required for the transition from weak to strong adhesion; actin cytoskeleton fails to insert into peripheral E-cadherin plaques when p120ctn is uncoupled; p120ctn is metabolically stable and present at high cytoplasmic levels in cadherin-deficient cells.","method":"Stable transfection into E-cadherin-deficient cell lines, aggregation assays, detergent-free subcellular fractionation, actin cytoskeleton immunofluorescence","journal":"The Journal of cell biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — minimal point mutations uncoupling interaction combined with multiple functional readouts; independently replicated","pmids":["10629228"],"is_preprint":false},{"year":2000,"finding":"RPTPmu associates with p120ctn independently of cadherins, via its juxtamembrane region and second phosphatase domain; RPTPmu dephosphorylates tyrosine-phosphorylated p120ctn both in vitro and in intact cells; the RPTPmu-interacting domain of p120ctn maps to its unique N-terminus distinct from the cadherin-interacting domain.","method":"Co-immunoprecipitation, in vitro dephosphorylation assay, mutational analysis, cell-based phosphorylation assay","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — in vitro enzyme assay combined with in-cell validation and domain mapping by mutagenesis","pmids":["10753936"],"is_preprint":false},{"year":2000,"finding":"ARVCF competes with p120ctn for interaction with the E-cadherin juxtamembrane domain in a mutually exclusive manner; the branching phenotype activity of p120ctn maps to its Armadillo repeat domain (shown by ARVCF/p120 chimeras).","method":"Co-immunoprecipitation, ARVCF/p120 chimera transfection, immunofluorescence","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — reciprocal Co-IP and chimera analysis, single lab","pmids":["10725230"],"is_preprint":false},{"year":2001,"finding":"Src phosphorylates p120ctn at eight specific tyrosine sites identified by two-dimensional tryptic mapping and mutagenesis; an 8F mutant (all eight sites changed to phenylalanine) cannot be efficiently phosphorylated by Src and fails to interact with the tyrosine phosphatase SHP-1.","method":"2D tryptic phosphopeptide mapping, site-directed mutagenesis (Y→F), in vitro and in vivo Src kinase assays, co-immunoprecipitation with SHP-1","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 1 / Strong — phosphosite mapping confirmed by mutagenesis both in vitro and in vivo, multiple orthogonal methods","pmids":["11382764"],"is_preprint":false},{"year":2001,"finding":"Tyrosine phosphorylation of p120ctn by v-Src depends on its association with E-cadherin and resulting membrane localization; tyrosine 217 phosphorylation is involved in v-Src-mediated reduction of E-cadherin adhesion activity.","method":"L cell stable transfection with E-cadherin constructs, v-Src expression, aggregation assays, Y217F point mutant analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — functional point mutant combined with adhesion assay, single lab","pmids":["11171320"],"is_preprint":false},{"year":2002,"finding":"Drosophila Rho1 binds directly to p120ctn (and alpha-catenin) in vitro, with binding mapping to distinct surface-exposed regions; both proteins co-immunoprecipitate with Rho1-containing complexes from embryo lysates; p120ctn activity suppresses Rho1 accumulation.","method":"In vitro binding assay, co-immunoprecipitation from embryo lysates, genetic analysis of Rho1 and p120ctn mutants","journal":"Development (Cambridge, England)","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro binding confirmed by Co-IP in vivo, Drosophila ortholog study","pmids":["12135916"],"is_preprint":false},{"year":2002,"finding":"DEP1 (CD148) receptor tyrosine phosphatase interacts with p120ctn (identified by substrate-trapping mutant D/A approach); the interaction occurs independently of E-cadherin in K562 cells lacking adherens junctions, suggesting a direct DEP1-p120ctn interaction.","method":"GST-fusion substrate-trapping pull-down, co-immunoprecipitation, immunofluorescence colocalization","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — substrate-trapping method plus cell line validation, single lab","pmids":["12370829"],"is_preprint":false},{"year":2002,"finding":"Specific sequences in the p120ctn N-terminus (containing Src phosphorylation sites) are required for both nuclear localization and the branching phenotype; isoform 4A (lacking N-terminal domain) cannot enter the nucleus and does not induce branching; exon-B-encoded sequences abolish the branching phenotype and exclude p120ctn from the nucleus.","method":"Transient transfection of isoform expression constructs into melanoma and keratinocyte cells, immunofluorescence, nuclear localization analysis","journal":"Journal of cell science","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — systematic isoform structure-function analysis, single lab","pmids":["11896187"],"is_preprint":false},{"year":2003,"finding":"p120ctn is not co-trafficked with E-cadherin through the Golgi but is recruited contextually to E-cadherin complexes only at the basolateral plasma membrane in polarized MDCK cells; a dileucine sorting motif (S1) in the E-cadherin juxtamembrane domain is required for basolateral targeting of E-cadherin, and when E-cadherin is missorted to the apical membrane, p120ctn is not co-missorted but cannot be recruited at the apical membrane.","method":"Cycloheximide chase, temperature block, immunofluorescence in polarized MDCK cells, E-cadherin deletion mutant (EcadΔS1) analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple pharmacological and genetic perturbations in polarized epithelia, single lab","pmids":["12923199"],"is_preprint":false},{"year":2004,"finding":"p120ctn siRNA knockdown results in a striking dose-dependent loss of endogenous cadherins, demonstrating that p120ctn is essential for cadherin stability and regulates cadherin turnover.","method":"siRNA-mediated knockdown, immunoblotting for cadherin levels","journal":"Seminars in cell & developmental biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — loss-of-function with defined molecular readout (cadherin levels), single lab review summarizing primary data","pmids":["15561585"],"is_preprint":false},{"year":2004,"finding":"An intact NLS in p120ctn is required for its nuclear translocation and for the inhibition of Kaiso-mediated transcriptional repression; the NLS (containing key lysines) was validated by its ability to direct nuclear localization of a heterologous beta-galactosidase-GFP fusion protein; mutating two key lysines inhibits both nuclear localization and the branching phenotype.","method":"NLS mutagenesis (K→A), heterologous NLS-GFP fusion protein nuclear import assay, minimal promoter transcriptional assays","journal":"Journal of cell science","confidence":"High","confidence_rationale":"Tier 1 / Strong — NLS validated autonomously in heterologous protein, functional consequence (Kaiso repression) demonstrated by promoter assay","pmids":["15138284"],"is_preprint":false},{"year":2004,"finding":"Cytoplasmic p120ctn in E-cadherin-deficient breast cancer cells promotes membranous protrusions and migratory activity; p120ctn siRNA knockdown promotes stress fiber formation, increases Rho-GTPase activity, and reduces migration in E-cadherin-deficient cells.","method":"RNAi knockdown, Rho-GTPase activity assays, morphology and migration analysis","journal":"The American journal of pathology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — RNAi with specific Rho-GTPase readout, single lab","pmids":["15161659"],"is_preprint":false},{"year":2004,"finding":"Cytoplasmic localization of p120ctn is caused by the absence of E-cadherin: re-expression of endogenous E-cadherin (by 5-Aza treatment) shifts p120ctn from cytoplasm to membrane; suppression of E-cadherin by Snail, E47, or Slug causes cytoplasmic p120ctn localization and isoform switching.","method":"5-azacytidine E-cadherin re-expression, stable transfection of transcriptional repressors, immunofluorescence","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — multiple orthogonal experimental manipulations, single lab","pmids":["15077190"],"is_preprint":false},{"year":2005,"finding":"Nuclear p120ctn inhibits Kaiso-mediated transcriptional repression of the matrilysin promoter; p120ctn inhibition of Kaiso-DNA binding and Kaiso-mediated repression requires nuclear translocation of p120ctn (NLS mutant is inactive); chromatin immunoprecipitation confirmed Kaiso association with the matrilysin promoter in vivo.","method":"Chromatin immunoprecipitation, minimal promoter transcription assays, RNAi depletion of Kaiso, KBS mutation, p120ctn NLS mutant","journal":"Experimental cell research","confidence":"High","confidence_rationale":"Tier 1 / Strong — ChIP plus promoter assays with multiple genetic controls (RNAi, KBS mutant, NLS mutant), single lab with multiple orthogonal methods","pmids":["15817151"],"is_preprint":false},{"year":2005,"finding":"trans-Interacting nectin inhibits non-trans-interacting E-cadherin endocytosis through afadin, which binds Rap1 activated by nectin trans-interaction, interacts with p120ctn, and strengthens p120ctn binding to E-cadherin, thereby reducing E-cadherin endocytosis.","method":"Cell-free endocytosis assay, co-immunoprecipitation, dominant-negative afadin mutant analysis","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cell-free assay plus cell-based validation, multiple protein interaction steps confirmed","pmids":["15857834"],"is_preprint":false},{"year":2006,"finding":"R-cadherin expression in A431 cells downregulates E- and P-cadherin via competition for p120ctn: ectopic R-cadherin competes for p120ctn binding, leading to increased clathrin-dependent endocytosis and degradation of E-cadherin.","method":"Stable transfection, co-immunoprecipitation, cadherin turnover assays, clathrin-dependent endocytosis inhibition","journal":"Oncogene","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — competition for p120ctn mechanistically linked to endocytosis, single lab","pmids":["16786001"],"is_preprint":false},{"year":2004,"finding":"Gα12 physically interacts with p120ctn and selectively abrogates the p120ctn-induced branching phenotype; Gα12 expression compensates for the reduction of Rho activity induced by p120ctn; the interaction was confirmed by co-immunoprecipitation and in vitro binding, and occurs independently of E-cadherin.","method":"Co-immunoprecipitation, in vitro binding, cell morphology analysis in multiple cell types, Rho activity assay","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — in vitro and in-cell binding confirmed with functional consequence, single lab","pmids":["15240885"],"is_preprint":false},{"year":2007,"finding":"p120ctn isoform 3A overexpression causes cytoplasmic accumulation and forms a complex with cyclin E and CDK2 at centrosomes during mitosis, leading to cyclin E stabilization, prolonged S phase, nucleophosmin Thr199 phosphorylation, and aberrant centrosome amplification.","method":"Overexpression of p120ctn 3A, confocal microscopy, co-immunoprecipitation with cyclin E/CDK2, synchronized cell cycle analysis, immunoblotting","journal":"Cancer research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — co-IP of functional complex combined with cell-cycle phenotypic analysis, single lab","pmids":["17942908"],"is_preprint":false},{"year":2009,"finding":"E-cadherin-bound p120ctn contributes to RhoA inactivation by favoring p190RhoGAP-RhoA association on the plasma membrane of melanoma cells; p190RhoGAP and p120ctn associate predominantly on the plasma membrane of E-cadherin-overexpressing cells.","method":"Co-immunoprecipitation, RhoA activity assays, Matrigel invasion assays in melanoma cells expressing E-cadherin","journal":"The Journal of biological chemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — biochemical association combined with functional GTPase activity assay, single lab","pmids":["19293150"],"is_preprint":false},{"year":2010,"finding":"Gα12 binds to the N-terminal region (amino acids 121–323) of p120ctn and downregulates Src family kinase-induced tyrosine phosphorylation of p120ctn via a RhoA-independent mechanism; activated Gα12 mutants uncoupled from RhoA still suppress p120ctn phosphorylation; dominant active RhoA does not reduce Src-induced p120ctn phosphorylation.","method":"Domain mapping with deletion mutants, co-immunoprecipitation, Src kinase phosphorylation assay, RhoA dominant-active mutant analysis","journal":"Experimental cell research","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — domain mapping combined with functional phosphorylation assay and RhoA epistasis, single lab","pmids":["20974127"],"is_preprint":false},{"year":2013,"finding":"N-cadherin regulates spatially polarized PI3K/Rac1 signaling through a specific N-cadherin–p120ctn complex; the N-cadherin–p120ctn complex excludes integrin α5 at intercellular junctions to suppress local PI3K and Rac1 activity; this is distinct from N-cadherin–β-catenin-mediated myosin IIa/actin polarization.","method":"FRET biosensors on micropatterned fibronectin strips, siRNA knockdown, fluorescence imaging in live cells","journal":"Nature communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — FRET-based live-cell signaling measurement with siRNA epistasis, single lab but multiple readouts","pmids":["23481397"],"is_preprint":false},{"year":2016,"finding":"mTOR-regulated PKCε phosphorylates catenin delta-1 at S268, which mediates cell-cell adhesion in astrocytes and controls the mesenchymal-to-epithelial transition; TSC astrocytes show hyperphosphorylation of S268 reversible by mTOR inhibitors.","method":"Phosphorylation site analysis in TSC patient tubers, mTOR inhibitor treatment (Torin1), PKCε activity assays, cell adhesion assays","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — specific phosphorylation site identified with kinase-pathway epistasis and functional adhesion readout, single lab","pmids":["27516388"],"is_preprint":false},{"year":2017,"finding":"The ubiquitin ligase Mib1 ubiquitinates CTNND1 at K547, attenuating Rac1 activation; Mib1-mediated ubiquitination of Ctnnd1 promotes persistent directional cell migration; knockdown of Ctnnd1 partially rescues posterior lateral line primordium cell migration defects in zebrafish mib1 mutants.","method":"Ubiquitination assay identifying K547 site, Rac1 activation assay, wound-closure migration assay in HeLa cells, zebrafish genetic epistasis","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1 / Strong — specific ubiquitination site identified biochemically, functional consequence validated in cultured cells and zebrafish in vivo with epistasis","pmids":["29078376"],"is_preprint":false},{"year":2019,"finding":"Reduced p120ctn expression is necessary and sufficient to re-localize pancreatic progenitors to the peripheral tip domain, where they acquire acinar fate; p120ctn regulates pancreatic organ architecture through differential E-cadherin-based cell sorting; the same mechanism balances alpha vs. beta cell fate during endocrine specification.","method":"Conditional mouse knockout, CRISPR/Cas9 in Xenopus, lineage tracing, cell sorting assays","journal":"Developmental cell","confidence":"High","confidence_rationale":"Tier 2 / Strong — loss-of-function in two animal models with defined cellular fate and organ architecture readouts","pmids":["30853440"],"is_preprint":false},{"year":2020,"finding":"p120ctn is required for neural tube closure and neurogenesis in mice; conditional deletion in Wnt1-expressing cells causes neural tube closure defects and craniofacial abnormalities associated with loss of N-cadherin, E-cadherin, β-catenin, cortactin, and Shroom3 at the apical side of neural folds; lateral neural fold sides lose p120ctn but retain N-cadherin and β-catenin.","method":"Conditional knockout mice (p120ctnfl/fl;Del-Cre and p120ctnfl/fl;Wnt1-Cre), rescue by ROSA26-p120ctn in ES cells, immunofluorescence","journal":"BMC developmental biology","confidence":"High","confidence_rationale":"Tier 2 / Strong — two conditional knockout models with defined molecular and developmental phenotypes, partial rescue experiment","pmids":["32741376"],"is_preprint":false},{"year":2022,"finding":"p120ctn protects β-catenin from GSK3β-ubiquitin-guided degradation, thereby activating Wnt signaling; inducible endothelial deletion of Ctnnd1 in mice causes FEVR-like phenotypes; GSK3β inhibitors rescue cell proliferation defects in CTNND1-depleted endothelial cells and increase vessel density in Ctnnd1-deficient mouse retinas.","method":"Inducible endothelial-specific Ctnnd1 knockout mice, unbiased proteomics, GSK3β inhibitor treatment (LiCl, CHIR-99021), retinal vascular phenotype analysis, double-heterozygous genetic interaction","journal":"JCI insight","confidence":"High","confidence_rationale":"Tier 2 / Strong — in vivo knockout with proteomics, pharmacological rescue, and double-heterozygous epistasis across multiple orthogonal methods","pmids":["35700046"],"is_preprint":false},{"year":1999,"finding":"BP180 (type XVII collagen) interacts with p120ctn isoforms 1–3 but not isoform 4 via an amino-terminal segment (aa 13–25) of BP180; the interacting domain of p120ctn is located immediately upstream from the Armadillo repeats (encoded by exons 5 and 6, subject to alternative splicing).","method":"Yeast two-hybrid, in vitro protein-protein interaction assay","journal":"Journal of cellular biochemistry","confidence":"Medium","confidence_rationale":"Tier 1 / Moderate — yeast two-hybrid confirmed by in vitro assay, single lab","pmids":["10321838"],"is_preprint":false},{"year":2001,"finding":"MUC1 cytoplasmic domain binds directly to p120ctn and induces nuclear localization of p120ctn, providing a membrane-to-nucleus signaling pathway.","method":"Co-immunoprecipitation, direct binding assay, immunofluorescence nuclear localization analysis","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — direct binding plus nuclear localization readout, single lab","pmids":["11181067"],"is_preprint":false},{"year":2024,"finding":"ESRP1/2 regulate alternative splicing of Ctnnd1; overexpression of ctnnd1 rescues morphogenesis of epithelial-derived structures in esrp1/2 zebrafish mutants, placing Ctnnd1 downstream of Esrp1/2 in palatogenesis.","method":"Zebrafish esrp1/2 mutant rescue by ctnnd1 overexpression, alternative splicing analysis, CRISPR/mutagenesis","journal":"Communications biology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — genetic epistasis rescue in zebrafish, single lab","pmids":["39179789"],"is_preprint":false},{"year":2021,"finding":"Cytoplasmic p120ctn activates Rac1/Cdc42→PAK1→ERK signaling to promote EGFR-TKI (gefitinib) resistance in lung cancer cells; inhibiting Cdc42/Rac1 prevents cytoplasmic p120ctn from activating PAK1; PAK1 downregulation attenuates ERK activation by cytoplasmic p120ctn.","method":"Immunoblotting, Rac1/Cdc42/PAK1/ERK activity assays, siRNA knockdown, MTT viability assay in HCC827 and PC9 cells","journal":"Applied immunohistochemistry & molecular morphology","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — pathway epistasis with defined molecular intermediates, single lab","pmids":["34412070"],"is_preprint":false}],"current_model":"p120ctn (CTNND1) is an Armadillo-repeat catenin that binds the juxtamembrane domain of classical cadherins to stabilize them against endocytosis and degradation, promotes strong cell-cell adhesion and cadherin clustering, regulates Rho-family GTPases (inhibiting RhoA, modulating Rac1/Cdc42) in a context-dependent manner, shuttles to the nucleus where it relieves Kaiso-mediated transcriptional repression, protects β-catenin from GSK3β-mediated degradation to sustain Wnt signaling, is phosphorylated by Src at defined tyrosine residues and ubiquitinated by Mib1 at K547 to modulate Rac1 activity, and is subject to nuclear export via a leucine-rich NES encoded by alternatively spliced exon B, with its subcellular localization (membrane, cytoplasm, or nucleus) determining which of these distinct functions predominates."},"narrative":{"mechanistic_narrative":"CTNND1 (p120ctn) is an Armadillo-repeat catenin that functions as the central regulator of classical cadherin stability and cell-cell adhesion, binding directly through its Arm repeats to the juxtamembrane domain of E-, N-, and P-cadherins to drive ligand-dependent cadherin clustering and the transition from weak to strong adhesion [PMID:7651399, PMID:8660921, PMID:9566976, PMID:10629228]. p120ctn binding stabilizes cadherins against turnover: its depletion causes dose-dependent loss of endogenous cadherins, and competition for p120ctn binding by other cadherins drives clathrin-dependent cadherin endocytosis and degradation [PMID:15561585, PMID:16786001]. The protein's localization is dictated by cadherin availability — loss of E-cadherin or its repression by EMT transcription factors shifts p120ctn into the cytoplasm, where it controls Rho-family GTPase signaling, inhibiting RhoA via membrane recruitment of p190RhoGAP and modulating Rac1/Cdc42 activity in a context-dependent manner [PMID:15161659, PMID:15077190, PMID:19293150, PMID:23481397]. Nuclear/cytoplasmic partitioning is governed by an autonomous NLS and an exon-B-encoded leucine-rich NES; nuclear p120ctn binds the transcriptional repressor Kaiso through its Arm repeats and relieves Kaiso-mediated repression of target promoters such as matrilysin [PMID:10207085, PMID:10393933, PMID:15138284, PMID:15817151]. p120ctn is heavily regulated by phosphorylation — Src phosphorylates eight defined tyrosine residues, an activity counteracted by associated tyrosine phosphatases (RPTPmu, DEP1) and by Gα12 — and by Mib1-mediated ubiquitination at K547, which attenuates Rac1 to promote directional migration [PMID:10753936, PMID:11382764, PMID:12370829, PMID:20974127, PMID:29078376]. Beyond adhesion, p120ctn protects β-catenin from GSK3β-directed degradation to sustain Wnt signaling, and is required in vivo for neural tube closure, craniofacial and pancreatic morphogenesis, and retinal vascular development [PMID:30853440, PMID:32741376, PMID:35700046].","teleology":[{"year":1994,"claim":"Established that p120ctn is a bona fide member of the cadherin-catenin complex rather than an unrelated phosphoprotein, defining its physical home at adherens junctions.","evidence":"Co-IP, immunofluorescence colocalization, and immunoblotting in MDCK and Src-transformed MDCK cells","pmids":["7526156"],"confidence":"High","gaps":["Did not map the binding interface or distinguish direct from indirect association","Functional consequence of Src-induced tyrosine phosphorylation unresolved"]},{"year":1995,"claim":"Resolved whether p120ctn binds cadherin directly, showing its Arm repeats 1-10 bind E-cadherin independently of alpha-catenin.","evidence":"Yeast two-hybrid with domain mapping across multiple carcinoma cell lines","pmids":["7651399"],"confidence":"High","gaps":["Did not localize the binding site on the cadherin tail","Functional role of the interaction not yet defined"]},{"year":1998,"claim":"Localized the cadherin binding site to the juxtamembrane domain and tied p120ctn to adhesive strengthening, connecting binding to function.","evidence":"Affinity purification of juxtamembrane-binding proteins plus flow-detachment and aggregation assays in the Xenopus C-cadherin system","pmids":["9566976"],"confidence":"High","gaps":["Mechanism linking p120ctn binding to clustering not molecularly resolved"]},{"year":1998,"claim":"Defined the genomic complexity of CTNND1, revealing extensive isoform diversity from alternative start codons and spliced exons that would later explain functional divergence.","evidence":"cDNA cloning, exon mapping, RT-PCR isoform analysis","pmids":["9653641"],"confidence":"Medium","gaps":["Functional differences between isoforms not addressed in this study","Tissue distribution of isoforms not quantified"]},{"year":1999,"claim":"Identified a nuclear function by discovering p120ctn binds the transcription factor Kaiso, the first link to gene regulation distinct from adhesion.","evidence":"Yeast two-hybrid screen with domain mapping, reciprocal Co-IP, and immunolocalization","pmids":["10207085"],"confidence":"High","gaps":["Did not yet show transcriptional consequence of the interaction","Did not establish how p120ctn enters the nucleus"]},{"year":1999,"claim":"Explained nucleocytoplasmic partitioning by identifying an exon-B-encoded leucine-rich NES and showing E-cadherin sequesters p120ctn out of the nucleus.","evidence":"Isoform overexpression, NES-fusion microinjection, leptomycin B sensitivity, and PKC activation in carcinoma cell lines","pmids":["10393933"],"confidence":"High","gaps":["Import machinery not yet defined","Physiological signals controlling shuttling incompletely mapped"]},{"year":1999,"claim":"Showed p120ctn binding can negatively regulate adhesion, indicating its effect on cadherins is bidirectional and phosphorylation-dependent.","evidence":"Deletion-construct transfection, aggregation assays, and staurosporine treatment","pmids":["10409703"],"confidence":"Medium","gaps":["Identity of the regulatory N-terminal phosphosites not resolved here","Single-lab functional model"]},{"year":2000,"claim":"Established causality between p120ctn binding and strong adhesion by selectively uncoupling p120ctn from E-cadherin and observing loss of adhesion and actin recruitment.","evidence":"Minimal juxtamembrane point mutations in E-cadherin-deficient cells, aggregation assays, fractionation, and actin imaging","pmids":["10629228"],"confidence":"High","gaps":["Mechanism of actin insertion into cadherin plaques not defined"]},{"year":2000,"claim":"Identified phosphatases and competing catenins that regulate p120ctn, defining RPTPmu as a direct dephosphorylating enzyme and ARVCF as a mutually exclusive competitor.","evidence":"In vitro dephosphorylation assays, Co-IP, domain mapping, and ARVCF/p120 chimera analysis","pmids":["10753936","10725230"],"confidence":"High","gaps":["Physiological balance between p120ctn and ARVCF at junctions unquantified","RPTPmu-regulated downstream events not traced"]},{"year":2001,"claim":"Mapped the Src phosphorylation code on p120ctn and linked specific sites to adhesion regulation and phosphatase recruitment.","evidence":"2D tryptic phosphopeptide mapping, Y-to-F mutagenesis, in vitro/in vivo kinase assays, and Y217F adhesion assays","pmids":["11382764","11171320"],"confidence":"High","gaps":["Combinatorial logic of the eight sites not fully deconvoluted","Downstream effectors of each phosphosite incompletely defined"]},{"year":2002,"claim":"Connected p120ctn to Rho-GTPase control, showing direct Rho1 binding and suppression of Rho1 accumulation in Drosophila.","evidence":"In vitro binding, Co-IP from embryo lysates, and genetic analysis of Rho1/p120ctn mutants","pmids":["12135916"],"confidence":"Medium","gaps":["Mechanism of Rho suppression (GAP/GDI recruitment) not resolved here","Ortholog study; mammalian generality not yet shown"]},{"year":2003,"claim":"Clarified that p120ctn is not co-trafficked with cadherin but recruited contextually at the basolateral membrane, defining the spatial logic of complex assembly.","evidence":"Cycloheximide chase, temperature block, and E-cadherin sorting-mutant analysis in polarized MDCK cells","pmids":["12923199"],"confidence":"Medium","gaps":["Signal triggering basolateral recruitment not identified","Single-lab study"]},{"year":2004,"claim":"Demonstrated that p120ctn is essential for cadherin stability, establishing its set-point control over surface cadherin levels.","evidence":"Dose-dependent siRNA knockdown with cadherin immunoblotting","pmids":["15561585"],"confidence":"Medium","gaps":["Endocytic machinery mediating cadherin loss not defined in this report"]},{"year":2004,"claim":"Linked cytoplasmic p120ctn to migration and Rho-GTPase activity and showed E-cadherin loss redirects p120ctn to the cytoplasm, unifying localization and function.","evidence":"RNAi, Rho-GTPase activity assays, and migration/morphology analysis; E-cadherin re-expression and repressor transfection","pmids":["15161659","15077190"],"confidence":"Medium","gaps":["Direct GEF/GAP effectors of cytoplasmic p120ctn not resolved","Isoform identity of cytoplasmic pool not fully defined"]},{"year":2004,"claim":"Identified Gα12 as a binding partner that suppresses the p120ctn branching phenotype and compensates for p120ctn-induced Rho reduction.","evidence":"Co-IP, in vitro binding, Rho activity assays, and morphology analysis","pmids":["15240885"],"confidence":"Medium","gaps":["Physiological context of Gα12-p120ctn signaling unclear","Single-lab study"]},{"year":2004,"claim":"Demonstrated that nuclear translocation via an autonomous NLS is required for p120ctn to relieve Kaiso-mediated transcriptional repression, mechanistically coupling shuttling to gene regulation.","evidence":"NLS mutagenesis, heterologous NLS-GFP import assay, and minimal-promoter transcription assays","pmids":["15138284"],"confidence":"High","gaps":["Import receptor for the NLS not identified","Breadth of Kaiso target genes not defined here"]},{"year":2005,"claim":"Confirmed the nuclear function at an endogenous promoter, showing nuclear p120ctn blocks Kaiso-DNA binding and de-represses the matrilysin gene.","evidence":"ChIP, promoter assays, Kaiso RNAi, KBS and NLS mutants","pmids":["15817151"],"confidence":"High","gaps":["Genome-wide Kaiso/p120ctn target set not mapped"]},{"year":2005,"claim":"Placed p120ctn within nectin/afadin-Rap1 control of cadherin endocytosis, showing afadin strengthens p120ctn-E-cadherin binding to reduce internalization.","evidence":"Cell-free endocytosis assay, Co-IP, and dominant-negative afadin analysis","pmids":["15857834"],"confidence":"Medium","gaps":["Quantitative contribution relative to direct p120ctn capping unclear"]},{"year":2007,"claim":"Revealed a non-junctional role for cytoplasmic isoform 3A in cell-cycle and centrosome control via a cyclin E/CDK2 complex.","evidence":"Isoform overexpression, confocal imaging, Co-IP, and synchronized cell-cycle analysis","pmids":["17942908"],"confidence":"Medium","gaps":["Whether endogenous p120ctn performs this role at physiological levels unclear","Single-lab overexpression study"]},{"year":2009,"claim":"Defined a molecular mechanism for RhoA inactivation by membrane p120ctn through favoring p190RhoGAP-RhoA association.","evidence":"Co-IP, RhoA activity assays, and invasion assays in E-cadherin-expressing melanoma cells","pmids":["19293150"],"confidence":"Medium","gaps":["Direct vs. scaffold-mediated p190RhoGAP recruitment not distinguished"]},{"year":2010,"claim":"Showed Gα12 suppresses Src-induced p120ctn tyrosine phosphorylation via a RhoA-independent mechanism, separating Gα12's adhesion and phosphorylation effects.","evidence":"Domain mapping, Co-IP, Src kinase assays, and RhoA epistasis","pmids":["20974127"],"confidence":"Medium","gaps":["Mechanism by which Gα12 blocks Src access not defined"]},{"year":2013,"claim":"Demonstrated a specific N-cadherin-p120ctn complex spatially restricts PI3K/Rac1 signaling by excluding integrin α5, defining a discrete signaling output of this catenin pool.","evidence":"FRET biosensors on micropatterned fibronectin with siRNA epistasis in live cells","pmids":["23481397"],"confidence":"Medium","gaps":["Molecular basis for integrin exclusion not resolved","Single-lab study"]},{"year":2016,"claim":"Identified mTOR-PKCε phosphorylation of p120ctn at S268 controlling adhesion and mesenchymal-to-epithelial transition, with relevance to TSC.","evidence":"Phosphosite analysis in TSC tubers, Torin1 treatment, PKCε activity, and adhesion assays","pmids":["27516388"],"confidence":"Medium","gaps":["Downstream effectors of S268 phosphorylation not mapped","Single-lab study"]},{"year":2017,"claim":"Identified Mib1-mediated ubiquitination at K547 as a switch attenuating Rac1 to drive persistent directional migration, validated across cells and zebrafish.","evidence":"Ubiquitination site mapping, Rac1 activation assays, wound-closure migration, and zebrafish genetic epistasis","pmids":["29078376"],"confidence":"High","gaps":["Structural consequence of K547 ubiquitination on Rac1 regulation unknown"]},{"year":2019,"claim":"Established a developmental role in which p120ctn dosage drives differential E-cadherin-based cell sorting to specify pancreatic architecture and cell fate.","evidence":"Conditional mouse knockout, Xenopus CRISPR, lineage tracing, and cell-sorting assays","pmids":["30853440"],"confidence":"High","gaps":["Molecular link between p120ctn dosage and sorting strength not fully resolved"]},{"year":2020,"claim":"Demonstrated p120ctn is required for neural tube closure and stabilizes an apical cadherin-cortactin-Shroom3 module in cranial neural folds.","evidence":"Conditional knockout mice with ES-cell rescue and immunofluorescence","pmids":["32741376"],"confidence":"High","gaps":["Direct vs. cadherin-stability-dependent contribution to Shroom3 localization unclear"]},{"year":2022,"claim":"Identified a Wnt-pathway role in which p120ctn protects β-catenin from GSK3β-directed degradation, with loss causing FEVR-like retinal vascular defects rescuable by GSK3β inhibition.","evidence":"Inducible endothelial knockout mice, proteomics, GSK3β inhibitor rescue, and double-heterozygous epistasis","pmids":["35700046"],"confidence":"High","gaps":["Mechanism by which p120ctn shields β-catenin from the destruction complex not structurally defined"]},{"year":2024,"claim":"Placed Ctnnd1 downstream of ESRP1/2-mediated alternative splicing in epithelial morphogenesis and palatogenesis, linking isoform control to development.","evidence":"Zebrafish esrp1/2 mutant rescue by ctnnd1 overexpression and splicing analysis","pmids":["39179789"],"confidence":"Medium","gaps":["Which specific isoform drives the rescue not pinpointed"]},{"year":null,"claim":"How the distinct phosphorylation, ubiquitination, and splicing inputs are integrated to select among p120ctn's adhesion, GTPase, transcriptional, and Wnt functions at a structural level remains unresolved.","evidence":"","pmids":[],"confidence":"Medium","gaps":["No structural model linking modification state to localization choice","Isoform-specific function in vivo incompletely defined","Genome-wide map of nuclear p120ctn/Kaiso targets lacking"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0008092","term_label":"cytoskeletal protein binding","supporting_discovery_ids":[1,3,8]},{"term_id":"GO:0098631","term_label":"cell adhesion mediator activity","supporting_discovery_ids":[3,8,17]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[5,18,21]},{"term_id":"GO:0098772","term_label":"molecular function regulator activity","supporting_discovery_ids":[13,19,26,30]},{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[3,22]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0,3,16,26]},{"term_id":"GO:0005829","term_label":"cytosol","supporting_discovery_ids":[8,19,20]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[5,7,18,21]},{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[25]}],"pathway":[{"term_id":"R-HSA-1500931","term_label":"Cell-Cell communication","supporting_discovery_ids":[3,8,17]},{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[19,26,28,30]},{"term_id":"R-HSA-74160","term_label":"Gene expression (Transcription)","supporting_discovery_ids":[5,18,21]},{"term_id":"R-HSA-1266738","term_label":"Developmental Biology","supporting_discovery_ids":[31,32,33]}],"complexes":["cadherin-catenin complex (adherens junction)"],"partners":["CDH1","CDH2","ZBTB33","ARVCF","PTPRM","GNA12","MIB1","CTNNB1"],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"O60716","full_name":"Catenin delta-1","aliases":["Cadherin-associated Src substrate","CAS","p120 catenin","p120(ctn)","p120(cas)"],"length_aa":968,"mass_kda":108.2,"function":"Key regulator of cell-cell adhesion that associates with and regulates the cell adhesion properties of both C-, E- and N-cadherins, being critical for their surface stability (PubMed:14610055, PubMed:20371349). Promotes localization and retention of DSG3 at cell-cell junctions, via its interaction with DSG3 (PubMed:18343367). Beside cell-cell adhesion, regulates gene transcription through several transcription factors including ZBTB33/Kaiso2 and GLIS2, and the activity of Rho family GTPases and downstream cytoskeletal dynamics (PubMed:10207085, PubMed:20371349). Implicated both in cell transformation by SRC and in ligand-induced receptor signaling through the EGF, PDGF, CSF-1 and ERBB2 receptors (PubMed:17344476)","subcellular_location":"Cytoplasm","url":"https://www.uniprot.org/uniprotkb/O60716/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/CTNND1","classification":"Not Classified","n_dependent_lines":70,"n_total_lines":1208,"dependency_fraction":0.057947019867549666},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"CTNNB1","stoichiometry":10.0},{"gene":"MIF","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/CTNND1","total_profiled":1310},"omim":[{"mim_id":"621483","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 85A; CCDC85A","url":"https://www.omim.org/entry/621483"},{"mim_id":"621283","title":"COILED-COIL DOMAIN-CONTAINING PROTEIN 85C; CCDC85C","url":"https://www.omim.org/entry/621283"},{"mim_id":"619149","title":"LESSEL-KREIENKAMP SYNDROME; LESKRES","url":"https://www.omim.org/entry/619149"},{"mim_id":"617685","title":"CADHERIN 26; CDH26","url":"https://www.omim.org/entry/617685"},{"mim_id":"617681","title":"BLEPHAROCHEILODONTIC SYNDROME 2; BCDS2","url":"https://www.omim.org/entry/617681"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Enhanced","locations":[{"location":"Plasma membrane","reliability":"Enhanced"},{"location":"Basal body","reliability":"Additional"}],"tissue_specificity":"Low tissue specificity","tissue_distribution":"Detected in all","driving_tissues":[],"url":"https://www.proteinatlas.org/search/CTNND1"},"hgnc":{"alias_symbol":["KIAA0384","p120","p120cas","p120ctn"],"prev_symbol":["CTNND"]},"alphafold":{"accession":"O60716","domains":[{"cath_id":"1.25.10.10","chopping":"366-501","consensus_level":"medium","plddt":97.9891,"start":366,"end":501},{"cath_id":"1.25.10,1.25.40","chopping":"521-598_653-710","consensus_level":"medium","plddt":95.7687,"start":521,"end":710},{"cath_id":"1.25.10.10","chopping":"711-850","consensus_level":"medium","plddt":92.4101,"start":711,"end":850}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/O60716","model_url":"https://alphafold.ebi.ac.uk/files/AF-O60716-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-O60716-F1-predicted_aligned_error_v6.png","plddt_mean":65.06},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=CTNND1","jax_strain_url":"https://www.jax.org/strain/search?query=CTNND1"},"sequence":{"accession":"O60716","fasta_url":"https://rest.uniprot.org/uniprotkb/O60716.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/O60716/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/O60716"}},"corpus_meta":[{"pmid":"9566976","id":"PMC_9566976","title":"The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn.","date":"1998","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/9566976","citation_count":463,"is_preprint":false},{"pmid":"7526156","id":"PMC_7526156","title":"Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes.","date":"1994","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/7526156","citation_count":431,"is_preprint":false},{"pmid":"10629228","id":"PMC_10629228","title":"Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion.","date":"2000","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10629228","citation_count":397,"is_preprint":false},{"pmid":"10207085","id":"PMC_10207085","title":"The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor.","date":"1999","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/10207085","citation_count":346,"is_preprint":false},{"pmid":"7651399","id":"PMC_7651399","title":"The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin.","date":"1995","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/7651399","citation_count":199,"is_preprint":false},{"pmid":"10225956","id":"PMC_10225956","title":"p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells.","date":"1999","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/10225956","citation_count":194,"is_preprint":false},{"pmid":"12135916","id":"PMC_12135916","title":"Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila.","date":"2002","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/12135916","citation_count":160,"is_preprint":false},{"pmid":"15077190","id":"PMC_15077190","title":"Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions.","date":"2004","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/15077190","citation_count":152,"is_preprint":false},{"pmid":"10409703","id":"PMC_10409703","title":"p120(ctn) binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity.","date":"1999","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10409703","citation_count":152,"is_preprint":false},{"pmid":"17028013","id":"PMC_17028013","title":"p120-ctn: A nexus for contextual signaling via Rho GTPases.","date":"2006","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17028013","citation_count":150,"is_preprint":false},{"pmid":"15833838","id":"PMC_15833838","title":"Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases.","date":"2005","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/15833838","citation_count":148,"is_preprint":false},{"pmid":"9653641","id":"PMC_9653641","title":"Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms.","date":"1998","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/9653641","citation_count":141,"is_preprint":false},{"pmid":"15857834","id":"PMC_15857834","title":"Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn.","date":"2005","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/15857834","citation_count":137,"is_preprint":false},{"pmid":"10393933","id":"PMC_10393933","title":"Nuclear localization of the p120(ctn) Armadillo-like catenin is counteracted by a nuclear export signal and by E-cadherin expression.","date":"1999","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/10393933","citation_count":136,"is_preprint":false},{"pmid":"8660921","id":"PMC_8660921","title":"The novel catenin p120cas binds classical cadherins and induces an unusual morphological phenotype in NIH3T3 fibroblasts.","date":"1996","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/8660921","citation_count":131,"is_preprint":false},{"pmid":"11382764","id":"PMC_11382764","title":"Identification of Src phosphorylation sites in the catenin p120ctn.","date":"2001","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/11382764","citation_count":126,"is_preprint":false},{"pmid":"8653709","id":"PMC_8653709","title":"Identification of murine p120 isoforms and heterogeneous expression of p120cas isoforms in human tumor cell lines.","date":"1996","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/8653709","citation_count":112,"is_preprint":false},{"pmid":"12635138","id":"PMC_12635138","title":"Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia.","date":"2003","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/12635138","citation_count":112,"is_preprint":false},{"pmid":"10753936","id":"PMC_10753936","title":"Receptor protein-tyrosine phosphatase RPTPmu binds to and dephosphorylates the catenin p120(ctn).","date":"2000","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10753936","citation_count":108,"is_preprint":false},{"pmid":"16294216","id":"PMC_16294216","title":"A role for Kaiso-p120ctn complexes in cancer?","date":"2005","source":"Nature reviews. Cancer","url":"https://pubmed.ncbi.nlm.nih.gov/16294216","citation_count":103,"is_preprint":false},{"pmid":"15817151","id":"PMC_15817151","title":"The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin.","date":"2005","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/15817151","citation_count":101,"is_preprint":false},{"pmid":"15561585","id":"PMC_15561585","title":"Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer.","date":"2004","source":"Seminars in cell & developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/15561585","citation_count":97,"is_preprint":false},{"pmid":"17050009","id":"PMC_17050009","title":"Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso.","date":"2006","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17050009","citation_count":97,"is_preprint":false},{"pmid":"15138284","id":"PMC_15138284","title":"NLS-dependent nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression.","date":"2004","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/15138284","citation_count":89,"is_preprint":false},{"pmid":"9422525","id":"PMC_9422525","title":"The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin.","date":"1998","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/9422525","citation_count":77,"is_preprint":false},{"pmid":"16226102","id":"PMC_16226102","title":"Increased expression of delta-catenin/neural plakophilin-related armadillo protein is associated with the down-regulation and redistribution of E-cadherin and p120ctn in human prostate cancer.","date":"2005","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/16226102","citation_count":77,"is_preprint":false},{"pmid":"10725230","id":"PMC_10725230","title":"ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes.","date":"2000","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/10725230","citation_count":77,"is_preprint":false},{"pmid":"15161659","id":"PMC_15161659","title":"Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer.","date":"2004","source":"The American journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/15161659","citation_count":74,"is_preprint":false},{"pmid":"11171320","id":"PMC_11171320","title":"Tyrosine phosphorylation of p120(ctn) in v-Src transfected L cells depends on its association with E-cadherin and reduces adhesion activity.","date":"2001","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11171320","citation_count":74,"is_preprint":false},{"pmid":"12370829","id":"PMC_12370829","title":"The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120(ctn).","date":"2002","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/12370829","citation_count":71,"is_preprint":false},{"pmid":"15107817","id":"PMC_15107817","title":"E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells.","date":"2004","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/15107817","citation_count":67,"is_preprint":false},{"pmid":"11521230","id":"PMC_11521230","title":"Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas.","date":"2001","source":"Human pathology","url":"https://pubmed.ncbi.nlm.nih.gov/11521230","citation_count":66,"is_preprint":false},{"pmid":"11896187","id":"PMC_11896187","title":"Specific sequences in p120ctn determine subcellular distribution of its multiple isoforms involved in cellular adhesion of normal and malignant epithelial cells.","date":"2002","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/11896187","citation_count":66,"is_preprint":false},{"pmid":"17030444","id":"PMC_17030444","title":"Diverse functions of p120ctn in tumors.","date":"2006","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/17030444","citation_count":62,"is_preprint":false},{"pmid":"27193094","id":"PMC_27193094","title":"Overexpression of CTNND1 in hepatocellular carcinoma promotes carcinous characters through activation of Wnt/β-catenin signaling.","date":"2016","source":"Journal of experimental & clinical cancer research : CR","url":"https://pubmed.ncbi.nlm.nih.gov/27193094","citation_count":60,"is_preprint":false},{"pmid":"28301459","id":"PMC_28301459","title":"Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1.","date":"2017","source":"Genetics in medicine : official journal of the American College of Medical Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28301459","citation_count":56,"is_preprint":false},{"pmid":"32839503","id":"PMC_32839503","title":"Melatonin promotes cardiomyocyte proliferation and heart repair in mice with myocardial infarction via miR-143-3p/Yap/Ctnnd1 signaling pathway.","date":"2020","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/32839503","citation_count":56,"is_preprint":false},{"pmid":"11181067","id":"PMC_11181067","title":"The Human DF3/MUC1 carcinoma-associated antigen signals nuclear localization of the catenin p120(ctn).","date":"2001","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/11181067","citation_count":55,"is_preprint":false},{"pmid":"12923199","id":"PMC_12923199","title":"Contextual binding of p120ctn to E-cadherin at the basolateral plasma membrane in polarized epithelia.","date":"2003","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/12923199","citation_count":53,"is_preprint":false},{"pmid":"17509776","id":"PMC_17509776","title":"Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human gastric epithelial cells.","date":"2007","source":"Pathology, research and practice","url":"https://pubmed.ncbi.nlm.nih.gov/17509776","citation_count":52,"is_preprint":false},{"pmid":"19293150","id":"PMC_19293150","title":"Overexpression of E-cadherin on melanoma cells inhibits chemokine-promoted invasion involving p190RhoGAP/p120ctn-dependent inactivation of RhoA.","date":"2009","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/19293150","citation_count":51,"is_preprint":false},{"pmid":"9627058","id":"PMC_9627058","title":"Production and characterization of monoclonal antibodies to the catenin p120ctn.","date":"1998","source":"Hybridoma","url":"https://pubmed.ncbi.nlm.nih.gov/9627058","citation_count":50,"is_preprint":false},{"pmid":"16786001","id":"PMC_16786001","title":"Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120(ctn).","date":"2006","source":"Oncogene","url":"https://pubmed.ncbi.nlm.nih.gov/16786001","citation_count":49,"is_preprint":false},{"pmid":"31081718","id":"PMC_31081718","title":"Hsa_circ_0002577 promotes endometrial carcinoma progression via regulating miR-197/CTNND1 axis and activating Wnt/β-catenin pathway.","date":"2019","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/31081718","citation_count":48,"is_preprint":false},{"pmid":"22201829","id":"PMC_22201829","title":"Functions of p120ctn isoforms in cell-cell adhesion and intracellular signaling.","date":"2012","source":"Frontiers in bioscience (Landmark edition)","url":"https://pubmed.ncbi.nlm.nih.gov/22201829","citation_count":46,"is_preprint":false},{"pmid":"29348693","id":"PMC_29348693","title":"Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome.","date":"2018","source":"European journal of human genetics : EJHG","url":"https://pubmed.ncbi.nlm.nih.gov/29348693","citation_count":46,"is_preprint":false},{"pmid":"11052263","id":"PMC_11052263","title":"The catenin, p120ctn, is a common membrane-associated protein in various epithelial and non-epithelial cells and tissues.","date":"2000","source":"Histochemistry and cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/11052263","citation_count":44,"is_preprint":false},{"pmid":"23481397","id":"PMC_23481397","title":"N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways.","date":"2013","source":"Nature communications","url":"https://pubmed.ncbi.nlm.nih.gov/23481397","citation_count":44,"is_preprint":false},{"pmid":"16207756","id":"PMC_16207756","title":"Rho1 regulates Drosophila adherens junctions independently of p120ctn.","date":"2005","source":"Development (Cambridge, England)","url":"https://pubmed.ncbi.nlm.nih.gov/16207756","citation_count":41,"is_preprint":false},{"pmid":"20593408","id":"PMC_20593408","title":"delta-Catenin promotes malignant phenotype of non-small cell lung cancer by non-competitive binding to E-cadherin with p120ctn in cytoplasm.","date":"2010","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/20593408","citation_count":41,"is_preprint":false},{"pmid":"31889897","id":"PMC_31889897","title":"SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway.","date":"2019","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/31889897","citation_count":38,"is_preprint":false},{"pmid":"35700046","id":"PMC_35700046","title":"CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt/cadherin axis.","date":"2022","source":"JCI insight","url":"https://pubmed.ncbi.nlm.nih.gov/35700046","citation_count":36,"is_preprint":false},{"pmid":"20556744","id":"PMC_20556744","title":"Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer.","date":"2010","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/20556744","citation_count":36,"is_preprint":false},{"pmid":"20668551","id":"PMC_20668551","title":"p120ctn and P-cadherin but not E-cadherin regulate cell motility and invasion of DU145 prostate cancer cells.","date":"2010","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/20668551","citation_count":35,"is_preprint":false},{"pmid":"11724896","id":"PMC_11724896","title":"Tissue distribution and cell type-specific expression of p120ctn isoforms.","date":"2001","source":"The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society","url":"https://pubmed.ncbi.nlm.nih.gov/11724896","citation_count":34,"is_preprint":false},{"pmid":"17942908","id":"PMC_17942908","title":"Cyclin-dependent kinase 2/cyclin E complex is involved in p120 catenin (p120ctn)-dependent cell growth control: a new role for p120ctn in cancer.","date":"2007","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/17942908","citation_count":33,"is_preprint":false},{"pmid":"32393764","id":"PMC_32393764","title":"The circular RNA circMAST1 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-1299 and regulating CTNND1 expression.","date":"2020","source":"Cell death & disease","url":"https://pubmed.ncbi.nlm.nih.gov/32393764","citation_count":31,"is_preprint":false},{"pmid":"29228664","id":"PMC_29228664","title":"Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1.","date":"2017","source":"Oncotarget","url":"https://pubmed.ncbi.nlm.nih.gov/29228664","citation_count":31,"is_preprint":false},{"pmid":"18490349","id":"PMC_18490349","title":"Nuclear targeting of beta-catenin and p120ctn during thrombin-induced endothelial barrier dysfunction.","date":"2008","source":"Cardiovascular research","url":"https://pubmed.ncbi.nlm.nih.gov/18490349","citation_count":31,"is_preprint":false},{"pmid":"32594834","id":"PMC_32594834","title":"Hsa-miR-425-5p promotes tumor growth and metastasis by activating the CTNND1-mediated β-catenin pathway and EMT in colorectal cancer.","date":"2020","source":"Cell cycle (Georgetown, Tex.)","url":"https://pubmed.ncbi.nlm.nih.gov/32594834","citation_count":31,"is_preprint":false},{"pmid":"10547572","id":"PMC_10547572","title":"Up-regulated cytoplasmic expression, with reduced membranous distribution, of the src substrate p120(ctn) in gastric carcinoma.","date":"1999","source":"The Journal of pathology","url":"https://pubmed.ncbi.nlm.nih.gov/10547572","citation_count":30,"is_preprint":false},{"pmid":"32196547","id":"PMC_32196547","title":"Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome.","date":"2020","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/32196547","citation_count":29,"is_preprint":false},{"pmid":"17047063","id":"PMC_17047063","title":"E-cadherin regulates human Nanos1, which interacts with p120ctn and induces tumor cell migration and invasion.","date":"2006","source":"Cancer research","url":"https://pubmed.ncbi.nlm.nih.gov/17047063","citation_count":29,"is_preprint":false},{"pmid":"34830862","id":"PMC_34830862","title":"Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone.","date":"2021","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/34830862","citation_count":28,"is_preprint":false},{"pmid":"30853440","id":"PMC_30853440","title":"p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate.","date":"2019","source":"Developmental cell","url":"https://pubmed.ncbi.nlm.nih.gov/30853440","citation_count":26,"is_preprint":false},{"pmid":"11855855","id":"PMC_11855855","title":"An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation.","date":"2002","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/11855855","citation_count":26,"is_preprint":false},{"pmid":"15836772","id":"PMC_15836772","title":"Recruitment of E-cadherin associated with alpha- and beta-catenins and p120ctn to the nectin-based cell-cell adhesion sites by the action of 12-O-tetradecanoylphorbol-13-acetate in MDCK cells.","date":"2005","source":"Genes to cells : devoted to molecular & cellular mechanisms","url":"https://pubmed.ncbi.nlm.nih.gov/15836772","citation_count":25,"is_preprint":false},{"pmid":"17614852","id":"PMC_17614852","title":"Reduction of p120(ctn) isoforms 1 and 3 is significantly associated with metastatic progression of human lung cancer.","date":"2007","source":"APMIS : acta pathologica, microbiologica, et immunologica Scandinavica","url":"https://pubmed.ncbi.nlm.nih.gov/17614852","citation_count":25,"is_preprint":false},{"pmid":"29990836","id":"PMC_29990836","title":"RETRACTED: MicroRNA-298 represses hepatocellular carcinoma progression by inhibiting CTNND1-mediated Wnt/β-catenin signaling.","date":"2018","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/29990836","citation_count":25,"is_preprint":false},{"pmid":"29078376","id":"PMC_29078376","title":"Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway.","date":"2017","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/29078376","citation_count":24,"is_preprint":false},{"pmid":"31913290","id":"PMC_31913290","title":"MicroRNA-96-5p represses breast cancer proliferation and invasion through Wnt/β-catenin signaling via targeting CTNND1.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31913290","citation_count":24,"is_preprint":false},{"pmid":"10321838","id":"PMC_10321838","title":"Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen.","date":"1999","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/10321838","citation_count":24,"is_preprint":false},{"pmid":"19615783","id":"PMC_19615783","title":"Kaiso is expressed in lung cancer: its expression and localization is affected by p120ctn.","date":"2009","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/19615783","citation_count":23,"is_preprint":false},{"pmid":"8808291","id":"PMC_8808291","title":"The gene encoding p120cas, a novel catenin, localizes on human chromosome 11q11 (CTNND) and mouse chromosome 2 (Catns).","date":"1996","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8808291","citation_count":21,"is_preprint":false},{"pmid":"10503270","id":"PMC_10503270","title":"Expression of catenins and p120cas in melanocytic nevi and cutaneous melanoma: deficient alpha-catenin expression is associated with melanoma progression.","date":"1999","source":"Pathology","url":"https://pubmed.ncbi.nlm.nih.gov/10503270","citation_count":20,"is_preprint":false},{"pmid":"33128584","id":"PMC_33128584","title":"Circular RNA circ_0000043 promotes endometrial carcinoma progression by regulating miR-1271-5p/CTNND1 axis.","date":"2020","source":"Archives of gynecology and obstetrics","url":"https://pubmed.ncbi.nlm.nih.gov/33128584","citation_count":20,"is_preprint":false},{"pmid":"11461664","id":"PMC_11461664","title":"Monoclonal antibodies to Kaiso: a novel transcription factor and p120ctn-binding protein.","date":"2001","source":"Hybridoma","url":"https://pubmed.ncbi.nlm.nih.gov/11461664","citation_count":20,"is_preprint":false},{"pmid":"24599758","id":"PMC_24599758","title":"Glial cell-derived neurotrophic factor attenuates neuropathic pain in a mouse model of chronic constriction injury: possible involvement of E-cadherin/p120ctn signaling.","date":"2014","source":"Journal of molecular neuroscience : MN","url":"https://pubmed.ncbi.nlm.nih.gov/24599758","citation_count":19,"is_preprint":false},{"pmid":"10650783","id":"PMC_10650783","title":"Expression patterns of the novel catenin p120cas in gastrointestinal cancers.","date":"1999","source":"Anticancer research","url":"https://pubmed.ncbi.nlm.nih.gov/10650783","citation_count":18,"is_preprint":false},{"pmid":"15240885","id":"PMC_15240885","title":"A role for Galpha12/Galpha13 in p120ctn regulation.","date":"2004","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/15240885","citation_count":18,"is_preprint":false},{"pmid":"10712269","id":"PMC_10712269","title":"Regulation of adherens junction protein p120(ctn) by 10 nM CCK precedes actin breakdown in rat pancreatic acini.","date":"2000","source":"American journal of physiology. Gastrointestinal and liver physiology","url":"https://pubmed.ncbi.nlm.nih.gov/10712269","citation_count":17,"is_preprint":false},{"pmid":"32760218","id":"PMC_32760218","title":"Long non-coding RNA KCNQ1OT1 up-regulates CTNND1 by sponging miR-329-3p to induce the proliferation, migration, invasion, and inhibit apoptosis of colorectal cancer cells.","date":"2020","source":"Cancer cell international","url":"https://pubmed.ncbi.nlm.nih.gov/32760218","citation_count":16,"is_preprint":false},{"pmid":"11389551","id":"PMC_11389551","title":"alpha-, beta-, gamma-catenin, and p120(CTN) expression during the terminal differentiation and fusion of human mononucleate cytotrophoblasts in vitro and in vivo.","date":"2001","source":"Molecular reproduction and development","url":"https://pubmed.ncbi.nlm.nih.gov/11389551","citation_count":15,"is_preprint":false},{"pmid":"29735970","id":"PMC_29735970","title":"Jinfu'an Decoction Inhibits Invasion and Metastasis in Human Lung Cancer Cells (H1650) via p120ctn-Mediated Induction and Kaiso.","date":"2018","source":"Medical science monitor : international medical journal of experimental and clinical research","url":"https://pubmed.ncbi.nlm.nih.gov/29735970","citation_count":13,"is_preprint":false},{"pmid":"26072075","id":"PMC_26072075","title":"Expressions of E-cadherin, p120ctn, β-catenin and NF-κB in ulcerative colitis.","date":"2015","source":"Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban","url":"https://pubmed.ncbi.nlm.nih.gov/26072075","citation_count":12,"is_preprint":false},{"pmid":"23981612","id":"PMC_23981612","title":"Heme oxygenase-1 promotes Caco-2 cell proliferation and migration by targeting CTNND1.","date":"2013","source":"Chinese medical journal","url":"https://pubmed.ncbi.nlm.nih.gov/23981612","citation_count":11,"is_preprint":false},{"pmid":"27516388","id":"PMC_27516388","title":"Catenin delta-1 (CTNND1) phosphorylation controls the mesenchymal to epithelial transition in astrocytic tumors.","date":"2016","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/27516388","citation_count":11,"is_preprint":false},{"pmid":"34784403","id":"PMC_34784403","title":"Black raspberry restores the expression of the tumor suppressor p120ctn in the oral cavity of mice treated with the carcinogen dibenzo[a,l]pyrene diol epoxide.","date":"2021","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/34784403","citation_count":10,"is_preprint":false},{"pmid":"38796558","id":"PMC_38796558","title":"CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions.","date":"2024","source":"Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association","url":"https://pubmed.ncbi.nlm.nih.gov/38796558","citation_count":9,"is_preprint":false},{"pmid":"25736925","id":"PMC_25736925","title":"C6orf106 enhances NSCLC cell invasion by upregulating vimentin, and downregulating E-cadherin and P120ctn.","date":"2015","source":"Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine","url":"https://pubmed.ncbi.nlm.nih.gov/25736925","citation_count":9,"is_preprint":false},{"pmid":"26926447","id":"PMC_26926447","title":"Increasing diagnostic accuracy to grade dysplasia in Barrett's esophagus using an immunohistochemical panel for CDX2, p120ctn, c-Myc and Jagged1.","date":"2016","source":"Diagnostic pathology","url":"https://pubmed.ncbi.nlm.nih.gov/26926447","citation_count":9,"is_preprint":false},{"pmid":"39179789","id":"PMC_39179789","title":"Functional analysis of ESRP1/2 gene variants and CTNND1 isoforms in orofacial cleft pathogenesis.","date":"2024","source":"Communications biology","url":"https://pubmed.ncbi.nlm.nih.gov/39179789","citation_count":8,"is_preprint":false},{"pmid":"17383052","id":"PMC_17383052","title":"Expression of E-cadherin, beta-catenin and p120ctn in the pulmonary sclerosing hemangioma.","date":"2007","source":"Lung cancer (Amsterdam, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/17383052","citation_count":8,"is_preprint":false},{"pmid":"38459187","id":"PMC_38459187","title":"EIF4A3-negatively driven circular RNA β-catenin (circβ-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis.","date":"2024","source":"British journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/38459187","citation_count":7,"is_preprint":false},{"pmid":"34412070","id":"PMC_34412070","title":"Cytoplasmic P120ctn Promotes Gefitinib Resistance in Lung Cancer Cells by Activating PAK1 and ERK Pathway.","date":"2021","source":"Applied immunohistochemistry & molecular morphology : AIMM","url":"https://pubmed.ncbi.nlm.nih.gov/34412070","citation_count":7,"is_preprint":false},{"pmid":"32741376","id":"PMC_32741376","title":"Neural defects caused by total and Wnt1-Cre mediated ablation of p120ctn in mice.","date":"2020","source":"BMC developmental biology","url":"https://pubmed.ncbi.nlm.nih.gov/32741376","citation_count":7,"is_preprint":false},{"pmid":"16534869","id":"PMC_16534869","title":"P120ctn overexpression enhances beta-catenin-E-cadherin binding and down regulates expression of survivin and cyclin D1 in BEL-7404 hepatoma cells.","date":"2006","source":"World journal of gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/16534869","citation_count":7,"is_preprint":false},{"pmid":"37686589","id":"PMC_37686589","title":"Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer.","date":"2023","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/37686589","citation_count":6,"is_preprint":false},{"pmid":"27146732","id":"PMC_27146732","title":"P120ctn may participate in epithelial-mesenchymal transition in OSCC.","date":"2016","source":"Indian journal of cancer","url":"https://pubmed.ncbi.nlm.nih.gov/27146732","citation_count":6,"is_preprint":false},{"pmid":"20974127","id":"PMC_20974127","title":"Gα(12) binds to the N-terminal regulatory domain of p120(ctn), and downregulates p120(ctn) tyrosine phosphorylation induced by Src family kinases via a RhoA independent mechanism.","date":"2010","source":"Experimental cell research","url":"https://pubmed.ncbi.nlm.nih.gov/20974127","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":51849,"output_tokens":8717,"usd":0.143151,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":18650,"output_tokens":7092,"usd":0.135275,"stage2_stop_reason":"end_turn"},"total_usd":0.278426,"stage1_batch_id":"msgbatch_01ACAxJQabDsht39JXeWG22d","stage2_batch_id":"msgbatch_01QEU22A9U5sbPTgsMzTmvSf","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1994,\n      \"finding\": \"p120ctn (p120cas) was identified as a new catenin that associates with the E-cadherin complex containing alpha-catenin, beta-catenin, and plakoglobin, and precisely colocalizes with E-cadherin and catenins in vivo; in Src-transformed MDCK cells, p120, beta-catenin, and plakoglobin were heavily phosphorylated on tyrosine, but the physical associations were not disrupted.\",\n      \"method\": \"Co-immunoprecipitation, immunofluorescence colocalization, immunoblotting in MDCK cells\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — reciprocal Co-IP and colocalization, foundational paper replicated extensively by subsequent work\",\n      \"pmids\": [\"7526156\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"p120ctn (CAS) binds directly to E-cadherin via its Arm repeats 1–10, independently of alpha-catenin, and does not interact with APC or alpha-catenin; direct interaction confirmed in yeast two-hybrid system.\",\n      \"method\": \"Yeast two-hybrid, cell line analysis (PC3, SW480, HCT116)\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — direct binding confirmed by yeast two-hybrid with domain mapping, replicated across multiple cell lines and subsequent studies\",\n      \"pmids\": [\"7651399\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1996,\n      \"finding\": \"p120ctn associates with N-cadherin and P-cadherin (not only E-cadherin) via its Armadillo repeat domain; overexpression in NIH3T3 cells induces a striking dendrite-like branching morphological phenotype dependent on an intact Arm domain.\",\n      \"method\": \"Co-immunoprecipitation, transfection of CAS mutants in MDCK and NIH3T3 cells, immunofluorescence\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — Co-IP across multiple cadherin types and domain-deletion mutant analysis, single lab\",\n      \"pmids\": [\"8660921\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"The juxtamembrane region of the cadherin cytoplasmic tail is the major binding site for p120ctn and is required for ligand-dependent cadherin clustering and adhesive strengthening; p120ctn was purified as the major protein binding this region.\",\n      \"method\": \"Affinity purification of proteins binding juxtamembrane region, deletion mutant analysis, laminar flow detachment assays, aggregation assays in Xenopus C-cadherin system\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — biochemical purification combined with functional adhesion assays, multiple orthogonal methods\",\n      \"pmids\": [\"9566976\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1998,\n      \"finding\": \"The human CTNND1 gene comprises 21 exons and encodes up to 32 protein isoforms via alternative splicing and multiple translation initiation codons; isoforms 1–4 differ by start codon used, with additional variation from alternatively spliced exons A, B, and C.\",\n      \"method\": \"cDNA cloning, exon mapping, RT-PCR isoform analysis\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic molecular cloning and transcript analysis, single lab but comprehensive\",\n      \"pmids\": [\"9653641\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"p120ctn interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor, via Arm repeats 1–7 of p120ctn and the C-terminal 200 amino acids of Kaiso; Kaiso localizes to the nucleus and co-precipitates specifically with p120ctn antibodies but not with antibodies to alpha- or beta-catenin, E-cadherin, or APC.\",\n      \"method\": \"Yeast two-hybrid screen, monoclonal antibody co-immunoprecipitation, immunolocalization in mammalian cells\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — yeast two-hybrid with domain mapping confirmed by reciprocal Co-IP and immunolocalization\",\n      \"pmids\": [\"10207085\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"p120ctn binds the membrane-proximal region of E-cadherin and negatively regulates adhesion activity; amino-terminally deleted p120ctn (lacking serine/threonine phosphorylation sites) activates nonfunctional E-cadherin; staurosporine-induced mobility shift of p120ctn correlates with cadherin activation and converts E-cadherin from cytochalasin D-sensitive to insensitive state.\",\n      \"method\": \"Deletion construct transfection, co-immunoprecipitation, aggregation assays, kinase inhibitor (staurosporine) treatment\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple functional assays with deletion mutants, single lab\",\n      \"pmids\": [\"10409703\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"p120ctn nuclear localization is counteracted by a leucine-rich nuclear export signal (NES) encoded by alternatively spliced exon B; expression of E-cadherin directs p120ctn out of the nucleus; nuclear export of exon-B-containing isoforms is sensitive to leptomycin B; PKC activation increases nuclear p120ctn.\",\n      \"method\": \"Overexpression of isoforms, microinjection of NES-carrier fusion proteins, leptomycin B treatment, immunofluorescence in multiple carcinoma cell lines\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — NES function validated autonomously by microinjection, multiple orthogonal methods in one study\",\n      \"pmids\": [\"10393933\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"Selective uncoupling of p120ctn from E-cadherin (via minimal juxtamembrane domain mutations) disrupts E-cadherin-mediated strong adhesion; p120ctn is required for the transition from weak to strong adhesion; actin cytoskeleton fails to insert into peripheral E-cadherin plaques when p120ctn is uncoupled; p120ctn is metabolically stable and present at high cytoplasmic levels in cadherin-deficient cells.\",\n      \"method\": \"Stable transfection into E-cadherin-deficient cell lines, aggregation assays, detergent-free subcellular fractionation, actin cytoskeleton immunofluorescence\",\n      \"journal\": \"The Journal of cell biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — minimal point mutations uncoupling interaction combined with multiple functional readouts; independently replicated\",\n      \"pmids\": [\"10629228\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"RPTPmu associates with p120ctn independently of cadherins, via its juxtamembrane region and second phosphatase domain; RPTPmu dephosphorylates tyrosine-phosphorylated p120ctn both in vitro and in intact cells; the RPTPmu-interacting domain of p120ctn maps to its unique N-terminus distinct from the cadherin-interacting domain.\",\n      \"method\": \"Co-immunoprecipitation, in vitro dephosphorylation assay, mutational analysis, cell-based phosphorylation assay\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — in vitro enzyme assay combined with in-cell validation and domain mapping by mutagenesis\",\n      \"pmids\": [\"10753936\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2000,\n      \"finding\": \"ARVCF competes with p120ctn for interaction with the E-cadherin juxtamembrane domain in a mutually exclusive manner; the branching phenotype activity of p120ctn maps to its Armadillo repeat domain (shown by ARVCF/p120 chimeras).\",\n      \"method\": \"Co-immunoprecipitation, ARVCF/p120 chimera transfection, immunofluorescence\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — reciprocal Co-IP and chimera analysis, single lab\",\n      \"pmids\": [\"10725230\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Src phosphorylates p120ctn at eight specific tyrosine sites identified by two-dimensional tryptic mapping and mutagenesis; an 8F mutant (all eight sites changed to phenylalanine) cannot be efficiently phosphorylated by Src and fails to interact with the tyrosine phosphatase SHP-1.\",\n      \"method\": \"2D tryptic phosphopeptide mapping, site-directed mutagenesis (Y→F), in vitro and in vivo Src kinase assays, co-immunoprecipitation with SHP-1\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — phosphosite mapping confirmed by mutagenesis both in vitro and in vivo, multiple orthogonal methods\",\n      \"pmids\": [\"11382764\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"Tyrosine phosphorylation of p120ctn by v-Src depends on its association with E-cadherin and resulting membrane localization; tyrosine 217 phosphorylation is involved in v-Src-mediated reduction of E-cadherin adhesion activity.\",\n      \"method\": \"L cell stable transfection with E-cadherin constructs, v-Src expression, aggregation assays, Y217F point mutant analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — functional point mutant combined with adhesion assay, single lab\",\n      \"pmids\": [\"11171320\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Drosophila Rho1 binds directly to p120ctn (and alpha-catenin) in vitro, with binding mapping to distinct surface-exposed regions; both proteins co-immunoprecipitate with Rho1-containing complexes from embryo lysates; p120ctn activity suppresses Rho1 accumulation.\",\n      \"method\": \"In vitro binding assay, co-immunoprecipitation from embryo lysates, genetic analysis of Rho1 and p120ctn mutants\",\n      \"journal\": \"Development (Cambridge, England)\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro binding confirmed by Co-IP in vivo, Drosophila ortholog study\",\n      \"pmids\": [\"12135916\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"DEP1 (CD148) receptor tyrosine phosphatase interacts with p120ctn (identified by substrate-trapping mutant D/A approach); the interaction occurs independently of E-cadherin in K562 cells lacking adherens junctions, suggesting a direct DEP1-p120ctn interaction.\",\n      \"method\": \"GST-fusion substrate-trapping pull-down, co-immunoprecipitation, immunofluorescence colocalization\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — substrate-trapping method plus cell line validation, single lab\",\n      \"pmids\": [\"12370829\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2002,\n      \"finding\": \"Specific sequences in the p120ctn N-terminus (containing Src phosphorylation sites) are required for both nuclear localization and the branching phenotype; isoform 4A (lacking N-terminal domain) cannot enter the nucleus and does not induce branching; exon-B-encoded sequences abolish the branching phenotype and exclude p120ctn from the nucleus.\",\n      \"method\": \"Transient transfection of isoform expression constructs into melanoma and keratinocyte cells, immunofluorescence, nuclear localization analysis\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — systematic isoform structure-function analysis, single lab\",\n      \"pmids\": [\"11896187\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2003,\n      \"finding\": \"p120ctn is not co-trafficked with E-cadherin through the Golgi but is recruited contextually to E-cadherin complexes only at the basolateral plasma membrane in polarized MDCK cells; a dileucine sorting motif (S1) in the E-cadherin juxtamembrane domain is required for basolateral targeting of E-cadherin, and when E-cadherin is missorted to the apical membrane, p120ctn is not co-missorted but cannot be recruited at the apical membrane.\",\n      \"method\": \"Cycloheximide chase, temperature block, immunofluorescence in polarized MDCK cells, E-cadherin deletion mutant (EcadΔS1) analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple pharmacological and genetic perturbations in polarized epithelia, single lab\",\n      \"pmids\": [\"12923199\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"p120ctn siRNA knockdown results in a striking dose-dependent loss of endogenous cadherins, demonstrating that p120ctn is essential for cadherin stability and regulates cadherin turnover.\",\n      \"method\": \"siRNA-mediated knockdown, immunoblotting for cadherin levels\",\n      \"journal\": \"Seminars in cell & developmental biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — loss-of-function with defined molecular readout (cadherin levels), single lab review summarizing primary data\",\n      \"pmids\": [\"15561585\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"An intact NLS in p120ctn is required for its nuclear translocation and for the inhibition of Kaiso-mediated transcriptional repression; the NLS (containing key lysines) was validated by its ability to direct nuclear localization of a heterologous beta-galactosidase-GFP fusion protein; mutating two key lysines inhibits both nuclear localization and the branching phenotype.\",\n      \"method\": \"NLS mutagenesis (K→A), heterologous NLS-GFP fusion protein nuclear import assay, minimal promoter transcriptional assays\",\n      \"journal\": \"Journal of cell science\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — NLS validated autonomously in heterologous protein, functional consequence (Kaiso repression) demonstrated by promoter assay\",\n      \"pmids\": [\"15138284\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Cytoplasmic p120ctn in E-cadherin-deficient breast cancer cells promotes membranous protrusions and migratory activity; p120ctn siRNA knockdown promotes stress fiber formation, increases Rho-GTPase activity, and reduces migration in E-cadherin-deficient cells.\",\n      \"method\": \"RNAi knockdown, Rho-GTPase activity assays, morphology and migration analysis\",\n      \"journal\": \"The American journal of pathology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — RNAi with specific Rho-GTPase readout, single lab\",\n      \"pmids\": [\"15161659\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Cytoplasmic localization of p120ctn is caused by the absence of E-cadherin: re-expression of endogenous E-cadherin (by 5-Aza treatment) shifts p120ctn from cytoplasm to membrane; suppression of E-cadherin by Snail, E47, or Slug causes cytoplasmic p120ctn localization and isoform switching.\",\n      \"method\": \"5-azacytidine E-cadherin re-expression, stable transfection of transcriptional repressors, immunofluorescence\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — multiple orthogonal experimental manipulations, single lab\",\n      \"pmids\": [\"15077190\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"Nuclear p120ctn inhibits Kaiso-mediated transcriptional repression of the matrilysin promoter; p120ctn inhibition of Kaiso-DNA binding and Kaiso-mediated repression requires nuclear translocation of p120ctn (NLS mutant is inactive); chromatin immunoprecipitation confirmed Kaiso association with the matrilysin promoter in vivo.\",\n      \"method\": \"Chromatin immunoprecipitation, minimal promoter transcription assays, RNAi depletion of Kaiso, KBS mutation, p120ctn NLS mutant\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — ChIP plus promoter assays with multiple genetic controls (RNAi, KBS mutant, NLS mutant), single lab with multiple orthogonal methods\",\n      \"pmids\": [\"15817151\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2005,\n      \"finding\": \"trans-Interacting nectin inhibits non-trans-interacting E-cadherin endocytosis through afadin, which binds Rap1 activated by nectin trans-interaction, interacts with p120ctn, and strengthens p120ctn binding to E-cadherin, thereby reducing E-cadherin endocytosis.\",\n      \"method\": \"Cell-free endocytosis assay, co-immunoprecipitation, dominant-negative afadin mutant analysis\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cell-free assay plus cell-based validation, multiple protein interaction steps confirmed\",\n      \"pmids\": [\"15857834\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"R-cadherin expression in A431 cells downregulates E- and P-cadherin via competition for p120ctn: ectopic R-cadherin competes for p120ctn binding, leading to increased clathrin-dependent endocytosis and degradation of E-cadherin.\",\n      \"method\": \"Stable transfection, co-immunoprecipitation, cadherin turnover assays, clathrin-dependent endocytosis inhibition\",\n      \"journal\": \"Oncogene\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — competition for p120ctn mechanistically linked to endocytosis, single lab\",\n      \"pmids\": [\"16786001\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2004,\n      \"finding\": \"Gα12 physically interacts with p120ctn and selectively abrogates the p120ctn-induced branching phenotype; Gα12 expression compensates for the reduction of Rho activity induced by p120ctn; the interaction was confirmed by co-immunoprecipitation and in vitro binding, and occurs independently of E-cadherin.\",\n      \"method\": \"Co-immunoprecipitation, in vitro binding, cell morphology analysis in multiple cell types, Rho activity assay\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — in vitro and in-cell binding confirmed with functional consequence, single lab\",\n      \"pmids\": [\"15240885\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2007,\n      \"finding\": \"p120ctn isoform 3A overexpression causes cytoplasmic accumulation and forms a complex with cyclin E and CDK2 at centrosomes during mitosis, leading to cyclin E stabilization, prolonged S phase, nucleophosmin Thr199 phosphorylation, and aberrant centrosome amplification.\",\n      \"method\": \"Overexpression of p120ctn 3A, confocal microscopy, co-immunoprecipitation with cyclin E/CDK2, synchronized cell cycle analysis, immunoblotting\",\n      \"journal\": \"Cancer research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — co-IP of functional complex combined with cell-cycle phenotypic analysis, single lab\",\n      \"pmids\": [\"17942908\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"E-cadherin-bound p120ctn contributes to RhoA inactivation by favoring p190RhoGAP-RhoA association on the plasma membrane of melanoma cells; p190RhoGAP and p120ctn associate predominantly on the plasma membrane of E-cadherin-overexpressing cells.\",\n      \"method\": \"Co-immunoprecipitation, RhoA activity assays, Matrigel invasion assays in melanoma cells expressing E-cadherin\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — biochemical association combined with functional GTPase activity assay, single lab\",\n      \"pmids\": [\"19293150\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"Gα12 binds to the N-terminal region (amino acids 121–323) of p120ctn and downregulates Src family kinase-induced tyrosine phosphorylation of p120ctn via a RhoA-independent mechanism; activated Gα12 mutants uncoupled from RhoA still suppress p120ctn phosphorylation; dominant active RhoA does not reduce Src-induced p120ctn phosphorylation.\",\n      \"method\": \"Domain mapping with deletion mutants, co-immunoprecipitation, Src kinase phosphorylation assay, RhoA dominant-active mutant analysis\",\n      \"journal\": \"Experimental cell research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — domain mapping combined with functional phosphorylation assay and RhoA epistasis, single lab\",\n      \"pmids\": [\"20974127\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"N-cadherin regulates spatially polarized PI3K/Rac1 signaling through a specific N-cadherin–p120ctn complex; the N-cadherin–p120ctn complex excludes integrin α5 at intercellular junctions to suppress local PI3K and Rac1 activity; this is distinct from N-cadherin–β-catenin-mediated myosin IIa/actin polarization.\",\n      \"method\": \"FRET biosensors on micropatterned fibronectin strips, siRNA knockdown, fluorescence imaging in live cells\",\n      \"journal\": \"Nature communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — FRET-based live-cell signaling measurement with siRNA epistasis, single lab but multiple readouts\",\n      \"pmids\": [\"23481397\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"mTOR-regulated PKCε phosphorylates catenin delta-1 at S268, which mediates cell-cell adhesion in astrocytes and controls the mesenchymal-to-epithelial transition; TSC astrocytes show hyperphosphorylation of S268 reversible by mTOR inhibitors.\",\n      \"method\": \"Phosphorylation site analysis in TSC patient tubers, mTOR inhibitor treatment (Torin1), PKCε activity assays, cell adhesion assays\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — specific phosphorylation site identified with kinase-pathway epistasis and functional adhesion readout, single lab\",\n      \"pmids\": [\"27516388\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"The ubiquitin ligase Mib1 ubiquitinates CTNND1 at K547, attenuating Rac1 activation; Mib1-mediated ubiquitination of Ctnnd1 promotes persistent directional cell migration; knockdown of Ctnnd1 partially rescues posterior lateral line primordium cell migration defects in zebrafish mib1 mutants.\",\n      \"method\": \"Ubiquitination assay identifying K547 site, Rac1 activation assay, wound-closure migration assay in HeLa cells, zebrafish genetic epistasis\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1 / Strong — specific ubiquitination site identified biochemically, functional consequence validated in cultured cells and zebrafish in vivo with epistasis\",\n      \"pmids\": [\"29078376\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2019,\n      \"finding\": \"Reduced p120ctn expression is necessary and sufficient to re-localize pancreatic progenitors to the peripheral tip domain, where they acquire acinar fate; p120ctn regulates pancreatic organ architecture through differential E-cadherin-based cell sorting; the same mechanism balances alpha vs. beta cell fate during endocrine specification.\",\n      \"method\": \"Conditional mouse knockout, CRISPR/Cas9 in Xenopus, lineage tracing, cell sorting assays\",\n      \"journal\": \"Developmental cell\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — loss-of-function in two animal models with defined cellular fate and organ architecture readouts\",\n      \"pmids\": [\"30853440\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2020,\n      \"finding\": \"p120ctn is required for neural tube closure and neurogenesis in mice; conditional deletion in Wnt1-expressing cells causes neural tube closure defects and craniofacial abnormalities associated with loss of N-cadherin, E-cadherin, β-catenin, cortactin, and Shroom3 at the apical side of neural folds; lateral neural fold sides lose p120ctn but retain N-cadherin and β-catenin.\",\n      \"method\": \"Conditional knockout mice (p120ctnfl/fl;Del-Cre and p120ctnfl/fl;Wnt1-Cre), rescue by ROSA26-p120ctn in ES cells, immunofluorescence\",\n      \"journal\": \"BMC developmental biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — two conditional knockout models with defined molecular and developmental phenotypes, partial rescue experiment\",\n      \"pmids\": [\"32741376\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2022,\n      \"finding\": \"p120ctn protects β-catenin from GSK3β-ubiquitin-guided degradation, thereby activating Wnt signaling; inducible endothelial deletion of Ctnnd1 in mice causes FEVR-like phenotypes; GSK3β inhibitors rescue cell proliferation defects in CTNND1-depleted endothelial cells and increase vessel density in Ctnnd1-deficient mouse retinas.\",\n      \"method\": \"Inducible endothelial-specific Ctnnd1 knockout mice, unbiased proteomics, GSK3β inhibitor treatment (LiCl, CHIR-99021), retinal vascular phenotype analysis, double-heterozygous genetic interaction\",\n      \"journal\": \"JCI insight\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 / Strong — in vivo knockout with proteomics, pharmacological rescue, and double-heterozygous epistasis across multiple orthogonal methods\",\n      \"pmids\": [\"35700046\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1999,\n      \"finding\": \"BP180 (type XVII collagen) interacts with p120ctn isoforms 1–3 but not isoform 4 via an amino-terminal segment (aa 13–25) of BP180; the interacting domain of p120ctn is located immediately upstream from the Armadillo repeats (encoded by exons 5 and 6, subject to alternative splicing).\",\n      \"method\": \"Yeast two-hybrid, in vitro protein-protein interaction assay\",\n      \"journal\": \"Journal of cellular biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 1 / Moderate — yeast two-hybrid confirmed by in vitro assay, single lab\",\n      \"pmids\": [\"10321838\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2001,\n      \"finding\": \"MUC1 cytoplasmic domain binds directly to p120ctn and induces nuclear localization of p120ctn, providing a membrane-to-nucleus signaling pathway.\",\n      \"method\": \"Co-immunoprecipitation, direct binding assay, immunofluorescence nuclear localization analysis\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — direct binding plus nuclear localization readout, single lab\",\n      \"pmids\": [\"11181067\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"ESRP1/2 regulate alternative splicing of Ctnnd1; overexpression of ctnnd1 rescues morphogenesis of epithelial-derived structures in esrp1/2 zebrafish mutants, placing Ctnnd1 downstream of Esrp1/2 in palatogenesis.\",\n      \"method\": \"Zebrafish esrp1/2 mutant rescue by ctnnd1 overexpression, alternative splicing analysis, CRISPR/mutagenesis\",\n      \"journal\": \"Communications biology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — genetic epistasis rescue in zebrafish, single lab\",\n      \"pmids\": [\"39179789\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Cytoplasmic p120ctn activates Rac1/Cdc42→PAK1→ERK signaling to promote EGFR-TKI (gefitinib) resistance in lung cancer cells; inhibiting Cdc42/Rac1 prevents cytoplasmic p120ctn from activating PAK1; PAK1 downregulation attenuates ERK activation by cytoplasmic p120ctn.\",\n      \"method\": \"Immunoblotting, Rac1/Cdc42/PAK1/ERK activity assays, siRNA knockdown, MTT viability assay in HCC827 and PC9 cells\",\n      \"journal\": \"Applied immunohistochemistry & molecular morphology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — pathway epistasis with defined molecular intermediates, single lab\",\n      \"pmids\": [\"34412070\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"p120ctn (CTNND1) is an Armadillo-repeat catenin that binds the juxtamembrane domain of classical cadherins to stabilize them against endocytosis and degradation, promotes strong cell-cell adhesion and cadherin clustering, regulates Rho-family GTPases (inhibiting RhoA, modulating Rac1/Cdc42) in a context-dependent manner, shuttles to the nucleus where it relieves Kaiso-mediated transcriptional repression, protects β-catenin from GSK3β-mediated degradation to sustain Wnt signaling, is phosphorylated by Src at defined tyrosine residues and ubiquitinated by Mib1 at K547 to modulate Rac1 activity, and is subject to nuclear export via a leucine-rich NES encoded by alternatively spliced exon B, with its subcellular localization (membrane, cytoplasm, or nucleus) determining which of these distinct functions predominates.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"CTNND1 (p120ctn) is an Armadillo-repeat catenin that functions as the central regulator of classical cadherin stability and cell-cell adhesion, binding directly through its Arm repeats to the juxtamembrane domain of E-, N-, and P-cadherins to drive ligand-dependent cadherin clustering and the transition from weak to strong adhesion [#1, #2, #3, #8]. p120ctn binding stabilizes cadherins against turnover: its depletion causes dose-dependent loss of endogenous cadherins, and competition for p120ctn binding by other cadherins drives clathrin-dependent cadherin endocytosis and degradation [#17, #23]. The protein's localization is dictated by cadherin availability — loss of E-cadherin or its repression by EMT transcription factors shifts p120ctn into the cytoplasm, where it controls Rho-family GTPase signaling, inhibiting RhoA via membrane recruitment of p190RhoGAP and modulating Rac1/Cdc42 activity in a context-dependent manner [#19, #20, #26, #28]. Nuclear/cytoplasmic partitioning is governed by an autonomous NLS and an exon-B-encoded leucine-rich NES; nuclear p120ctn binds the transcriptional repressor Kaiso through its Arm repeats and relieves Kaiso-mediated repression of target promoters such as matrilysin [#5, #7, #18, #21]. p120ctn is heavily regulated by phosphorylation — Src phosphorylates eight defined tyrosine residues, an activity counteracted by associated tyrosine phosphatases (RPTPmu, DEP1) and by Gα12 — and by Mib1-mediated ubiquitination at K547, which attenuates Rac1 to promote directional migration [#9, #11, #14, #27, #30]. Beyond adhesion, p120ctn protects β-catenin from GSK3β-directed degradation to sustain Wnt signaling, and is required in vivo for neural tube closure, craniofacial and pancreatic morphogenesis, and retinal vascular development [#31, #32, #33].\",\n  \"teleology\": [\n    {\n      \"year\": 1994,\n      \"claim\": \"Established that p120ctn is a bona fide member of the cadherin-catenin complex rather than an unrelated phosphoprotein, defining its physical home at adherens junctions.\",\n      \"evidence\": \"Co-IP, immunofluorescence colocalization, and immunoblotting in MDCK and Src-transformed MDCK cells\",\n      \"pmids\": [\"7526156\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not map the binding interface or distinguish direct from indirect association\", \"Functional consequence of Src-induced tyrosine phosphorylation unresolved\"]\n    },\n    {\n      \"year\": 1995,\n      \"claim\": \"Resolved whether p120ctn binds cadherin directly, showing its Arm repeats 1-10 bind E-cadherin independently of alpha-catenin.\",\n      \"evidence\": \"Yeast two-hybrid with domain mapping across multiple carcinoma cell lines\",\n      \"pmids\": [\"7651399\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not localize the binding site on the cadherin tail\", \"Functional role of the interaction not yet defined\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Localized the cadherin binding site to the juxtamembrane domain and tied p120ctn to adhesive strengthening, connecting binding to function.\",\n      \"evidence\": \"Affinity purification of juxtamembrane-binding proteins plus flow-detachment and aggregation assays in the Xenopus C-cadherin system\",\n      \"pmids\": [\"9566976\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism linking p120ctn binding to clustering not molecularly resolved\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Defined the genomic complexity of CTNND1, revealing extensive isoform diversity from alternative start codons and spliced exons that would later explain functional divergence.\",\n      \"evidence\": \"cDNA cloning, exon mapping, RT-PCR isoform analysis\",\n      \"pmids\": [\"9653641\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Functional differences between isoforms not addressed in this study\", \"Tissue distribution of isoforms not quantified\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Identified a nuclear function by discovering p120ctn binds the transcription factor Kaiso, the first link to gene regulation distinct from adhesion.\",\n      \"evidence\": \"Yeast two-hybrid screen with domain mapping, reciprocal Co-IP, and immunolocalization\",\n      \"pmids\": [\"10207085\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Did not yet show transcriptional consequence of the interaction\", \"Did not establish how p120ctn enters the nucleus\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Explained nucleocytoplasmic partitioning by identifying an exon-B-encoded leucine-rich NES and showing E-cadherin sequesters p120ctn out of the nucleus.\",\n      \"evidence\": \"Isoform overexpression, NES-fusion microinjection, leptomycin B sensitivity, and PKC activation in carcinoma cell lines\",\n      \"pmids\": [\"10393933\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Import machinery not yet defined\", \"Physiological signals controlling shuttling incompletely mapped\"]\n    },\n    {\n      \"year\": 1999,\n      \"claim\": \"Showed p120ctn binding can negatively regulate adhesion, indicating its effect on cadherins is bidirectional and phosphorylation-dependent.\",\n      \"evidence\": \"Deletion-construct transfection, aggregation assays, and staurosporine treatment\",\n      \"pmids\": [\"10409703\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Identity of the regulatory N-terminal phosphosites not resolved here\", \"Single-lab functional model\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Established causality between p120ctn binding and strong adhesion by selectively uncoupling p120ctn from E-cadherin and observing loss of adhesion and actin recruitment.\",\n      \"evidence\": \"Minimal juxtamembrane point mutations in E-cadherin-deficient cells, aggregation assays, fractionation, and actin imaging\",\n      \"pmids\": [\"10629228\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism of actin insertion into cadherin plaques not defined\"]\n    },\n    {\n      \"year\": 2000,\n      \"claim\": \"Identified phosphatases and competing catenins that regulate p120ctn, defining RPTPmu as a direct dephosphorylating enzyme and ARVCF as a mutually exclusive competitor.\",\n      \"evidence\": \"In vitro dephosphorylation assays, Co-IP, domain mapping, and ARVCF/p120 chimera analysis\",\n      \"pmids\": [\"10753936\", \"10725230\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Physiological balance between p120ctn and ARVCF at junctions unquantified\", \"RPTPmu-regulated downstream events not traced\"]\n    },\n    {\n      \"year\": 2001,\n      \"claim\": \"Mapped the Src phosphorylation code on p120ctn and linked specific sites to adhesion regulation and phosphatase recruitment.\",\n      \"evidence\": \"2D tryptic phosphopeptide mapping, Y-to-F mutagenesis, in vitro/in vivo kinase assays, and Y217F adhesion assays\",\n      \"pmids\": [\"11382764\", \"11171320\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Combinatorial logic of the eight sites not fully deconvoluted\", \"Downstream effectors of each phosphosite incompletely defined\"]\n    },\n    {\n      \"year\": 2002,\n      \"claim\": \"Connected p120ctn to Rho-GTPase control, showing direct Rho1 binding and suppression of Rho1 accumulation in Drosophila.\",\n      \"evidence\": \"In vitro binding, Co-IP from embryo lysates, and genetic analysis of Rho1/p120ctn mutants\",\n      \"pmids\": [\"12135916\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism of Rho suppression (GAP/GDI recruitment) not resolved here\", \"Ortholog study; mammalian generality not yet shown\"]\n    },\n    {\n      \"year\": 2003,\n      \"claim\": \"Clarified that p120ctn is not co-trafficked with cadherin but recruited contextually at the basolateral membrane, defining the spatial logic of complex assembly.\",\n      \"evidence\": \"Cycloheximide chase, temperature block, and E-cadherin sorting-mutant analysis in polarized MDCK cells\",\n      \"pmids\": [\"12923199\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Signal triggering basolateral recruitment not identified\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrated that p120ctn is essential for cadherin stability, establishing its set-point control over surface cadherin levels.\",\n      \"evidence\": \"Dose-dependent siRNA knockdown with cadherin immunoblotting\",\n      \"pmids\": [\"15561585\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Endocytic machinery mediating cadherin loss not defined in this report\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Linked cytoplasmic p120ctn to migration and Rho-GTPase activity and showed E-cadherin loss redirects p120ctn to the cytoplasm, unifying localization and function.\",\n      \"evidence\": \"RNAi, Rho-GTPase activity assays, and migration/morphology analysis; E-cadherin re-expression and repressor transfection\",\n      \"pmids\": [\"15161659\", \"15077190\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct GEF/GAP effectors of cytoplasmic p120ctn not resolved\", \"Isoform identity of cytoplasmic pool not fully defined\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Identified Gα12 as a binding partner that suppresses the p120ctn branching phenotype and compensates for p120ctn-induced Rho reduction.\",\n      \"evidence\": \"Co-IP, in vitro binding, Rho activity assays, and morphology analysis\",\n      \"pmids\": [\"15240885\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Physiological context of Gα12-p120ctn signaling unclear\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2004,\n      \"claim\": \"Demonstrated that nuclear translocation via an autonomous NLS is required for p120ctn to relieve Kaiso-mediated transcriptional repression, mechanistically coupling shuttling to gene regulation.\",\n      \"evidence\": \"NLS mutagenesis, heterologous NLS-GFP import assay, and minimal-promoter transcription assays\",\n      \"pmids\": [\"15138284\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Import receptor for the NLS not identified\", \"Breadth of Kaiso target genes not defined here\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Confirmed the nuclear function at an endogenous promoter, showing nuclear p120ctn blocks Kaiso-DNA binding and de-represses the matrilysin gene.\",\n      \"evidence\": \"ChIP, promoter assays, Kaiso RNAi, KBS and NLS mutants\",\n      \"pmids\": [\"15817151\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Genome-wide Kaiso/p120ctn target set not mapped\"]\n    },\n    {\n      \"year\": 2005,\n      \"claim\": \"Placed p120ctn within nectin/afadin-Rap1 control of cadherin endocytosis, showing afadin strengthens p120ctn-E-cadherin binding to reduce internalization.\",\n      \"evidence\": \"Cell-free endocytosis assay, Co-IP, and dominant-negative afadin analysis\",\n      \"pmids\": [\"15857834\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Quantitative contribution relative to direct p120ctn capping unclear\"]\n    },\n    {\n      \"year\": 2007,\n      \"claim\": \"Revealed a non-junctional role for cytoplasmic isoform 3A in cell-cycle and centrosome control via a cyclin E/CDK2 complex.\",\n      \"evidence\": \"Isoform overexpression, confocal imaging, Co-IP, and synchronized cell-cycle analysis\",\n      \"pmids\": [\"17942908\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Whether endogenous p120ctn performs this role at physiological levels unclear\", \"Single-lab overexpression study\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Defined a molecular mechanism for RhoA inactivation by membrane p120ctn through favoring p190RhoGAP-RhoA association.\",\n      \"evidence\": \"Co-IP, RhoA activity assays, and invasion assays in E-cadherin-expressing melanoma cells\",\n      \"pmids\": [\"19293150\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Direct vs. scaffold-mediated p190RhoGAP recruitment not distinguished\"]\n    },\n    {\n      \"year\": 2010,\n      \"claim\": \"Showed Gα12 suppresses Src-induced p120ctn tyrosine phosphorylation via a RhoA-independent mechanism, separating Gα12's adhesion and phosphorylation effects.\",\n      \"evidence\": \"Domain mapping, Co-IP, Src kinase assays, and RhoA epistasis\",\n      \"pmids\": [\"20974127\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Mechanism by which Gα12 blocks Src access not defined\"]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Demonstrated a specific N-cadherin-p120ctn complex spatially restricts PI3K/Rac1 signaling by excluding integrin α5, defining a discrete signaling output of this catenin pool.\",\n      \"evidence\": \"FRET biosensors on micropatterned fibronectin with siRNA epistasis in live cells\",\n      \"pmids\": [\"23481397\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Molecular basis for integrin exclusion not resolved\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identified mTOR-PKCε phosphorylation of p120ctn at S268 controlling adhesion and mesenchymal-to-epithelial transition, with relevance to TSC.\",\n      \"evidence\": \"Phosphosite analysis in TSC tubers, Torin1 treatment, PKCε activity, and adhesion assays\",\n      \"pmids\": [\"27516388\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Downstream effectors of S268 phosphorylation not mapped\", \"Single-lab study\"]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"Identified Mib1-mediated ubiquitination at K547 as a switch attenuating Rac1 to drive persistent directional migration, validated across cells and zebrafish.\",\n      \"evidence\": \"Ubiquitination site mapping, Rac1 activation assays, wound-closure migration, and zebrafish genetic epistasis\",\n      \"pmids\": [\"29078376\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Structural consequence of K547 ubiquitination on Rac1 regulation unknown\"]\n    },\n    {\n      \"year\": 2019,\n      \"claim\": \"Established a developmental role in which p120ctn dosage drives differential E-cadherin-based cell sorting to specify pancreatic architecture and cell fate.\",\n      \"evidence\": \"Conditional mouse knockout, Xenopus CRISPR, lineage tracing, and cell-sorting assays\",\n      \"pmids\": [\"30853440\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Molecular link between p120ctn dosage and sorting strength not fully resolved\"]\n    },\n    {\n      \"year\": 2020,\n      \"claim\": \"Demonstrated p120ctn is required for neural tube closure and stabilizes an apical cadherin-cortactin-Shroom3 module in cranial neural folds.\",\n      \"evidence\": \"Conditional knockout mice with ES-cell rescue and immunofluorescence\",\n      \"pmids\": [\"32741376\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Direct vs. cadherin-stability-dependent contribution to Shroom3 localization unclear\"]\n    },\n    {\n      \"year\": 2022,\n      \"claim\": \"Identified a Wnt-pathway role in which p120ctn protects β-catenin from GSK3β-directed degradation, with loss causing FEVR-like retinal vascular defects rescuable by GSK3β inhibition.\",\n      \"evidence\": \"Inducible endothelial knockout mice, proteomics, GSK3β inhibitor rescue, and double-heterozygous epistasis\",\n      \"pmids\": [\"35700046\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\"Mechanism by which p120ctn shields β-catenin from the destruction complex not structurally defined\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Placed Ctnnd1 downstream of ESRP1/2-mediated alternative splicing in epithelial morphogenesis and palatogenesis, linking isoform control to development.\",\n      \"evidence\": \"Zebrafish esrp1/2 mutant rescue by ctnnd1 overexpression and splicing analysis\",\n      \"pmids\": [\"39179789\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Which specific isoform drives the rescue not pinpointed\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"How the distinct phosphorylation, ubiquitination, and splicing inputs are integrated to select among p120ctn's adhesion, GTPase, transcriptional, and Wnt functions at a structural level remains unresolved.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"No structural model linking modification state to localization choice\", \"Isoform-specific function in vivo incompletely defined\", \"Genome-wide map of nuclear p120ctn/Kaiso targets lacking\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0008092\", \"supporting_discovery_ids\": [1, 3, 8]},\n      {\"term_id\": \"GO:0098631\", \"supporting_discovery_ids\": [3, 8, 17]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [5, 18, 21]},\n      {\"term_id\": \"GO:0098772\", \"supporting_discovery_ids\": [13, 19, 26, 30]},\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [3, 22]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0, 3, 16, 26]},\n      {\"term_id\": \"GO:0005829\", \"supporting_discovery_ids\": [8, 19, 20]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [5, 7, 18, 21]},\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [25]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-1500931\", \"supporting_discovery_ids\": [3, 8, 17]},\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [19, 26, 28, 30]},\n      {\"term_id\": \"R-HSA-74160\", \"supporting_discovery_ids\": [5, 18, 21]},\n      {\"term_id\": \"R-HSA-1266738\", \"supporting_discovery_ids\": [31, 32, 33]}\n    ],\n    \"complexes\": [\"cadherin-catenin complex (adherens junction)\"],\n    \"partners\": [\"CDH1\", \"CDH2\", \"ZBTB33\", \"ARVCF\", \"PTPRM\", \"GNA12\", \"MIB1\", \"CTNNB1\"],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":4,"faith_total":4,"faith_pct":100.0}}