Affinage

CTNND1

Catenin delta-1 · UniProt O60716

Length
968 aa
Mass
108.2 kDa
Annotated
2026-06-09
100 papers in source corpus 38 papers cited in narrative 38 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 4/4 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

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).

Mechanistic history

Synthesis pass · year-by-year structured walk · 28 steps
  1. 1994 High

    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

    PMID:7526156

    Open questions at the time
    • Did not map the binding interface or distinguish direct from indirect association
    • Functional consequence of Src-induced tyrosine phosphorylation unresolved
  2. 1995 High

    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

    PMID:7651399

    Open questions at the time
    • Did not localize the binding site on the cadherin tail
    • Functional role of the interaction not yet defined
  3. 1998 High

    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

    PMID:9566976

    Open questions at the time
    • Mechanism linking p120ctn binding to clustering not molecularly resolved
  4. 1998 Medium

    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

    PMID:9653641

    Open questions at the time
    • Functional differences between isoforms not addressed in this study
    • Tissue distribution of isoforms not quantified
  5. 1999 High

    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

    PMID:10207085

    Open questions at the time
    • Did not yet show transcriptional consequence of the interaction
    • Did not establish how p120ctn enters the nucleus
  6. 1999 High

    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

    PMID:10393933

    Open questions at the time
    • Import machinery not yet defined
    • Physiological signals controlling shuttling incompletely mapped
  7. 1999 Medium

    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

    PMID:10409703

    Open questions at the time
    • Identity of the regulatory N-terminal phosphosites not resolved here
    • Single-lab functional model
  8. 2000 High

    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

    PMID:10629228

    Open questions at the time
    • Mechanism of actin insertion into cadherin plaques not defined
  9. 2000 High

    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

    PMID:10725230 PMID:10753936

    Open questions at the time
    • Physiological balance between p120ctn and ARVCF at junctions unquantified
    • RPTPmu-regulated downstream events not traced
  10. 2001 High

    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

    PMID:11171320 PMID:11382764

    Open questions at the time
    • Combinatorial logic of the eight sites not fully deconvoluted
    • Downstream effectors of each phosphosite incompletely defined
  11. 2002 Medium

    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

    PMID:12135916

    Open questions at the time
    • Mechanism of Rho suppression (GAP/GDI recruitment) not resolved here
    • Ortholog study; mammalian generality not yet shown
  12. 2003 Medium

    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

    PMID:12923199

    Open questions at the time
    • Signal triggering basolateral recruitment not identified
    • Single-lab study
  13. 2004 Medium

    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

    PMID:15561585

    Open questions at the time
    • Endocytic machinery mediating cadherin loss not defined in this report
  14. 2004 Medium

    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

    PMID:15077190 PMID:15161659

    Open questions at the time
    • Direct GEF/GAP effectors of cytoplasmic p120ctn not resolved
    • Isoform identity of cytoplasmic pool not fully defined
  15. 2004 Medium

    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

    PMID:15240885

    Open questions at the time
    • Physiological context of Gα12-p120ctn signaling unclear
    • Single-lab study
  16. 2004 High

    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

    PMID:15138284

    Open questions at the time
    • Import receptor for the NLS not identified
    • Breadth of Kaiso target genes not defined here
  17. 2005 High

    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

    PMID:15817151

    Open questions at the time
    • Genome-wide Kaiso/p120ctn target set not mapped
  18. 2005 Medium

    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

    PMID:15857834

    Open questions at the time
    • Quantitative contribution relative to direct p120ctn capping unclear
  19. 2007 Medium

    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

    PMID:17942908

    Open questions at the time
    • Whether endogenous p120ctn performs this role at physiological levels unclear
    • Single-lab overexpression study
  20. 2009 Medium

    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

    PMID:19293150

    Open questions at the time
    • Direct vs. scaffold-mediated p190RhoGAP recruitment not distinguished
  21. 2010 Medium

    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

    PMID:20974127

    Open questions at the time
    • Mechanism by which Gα12 blocks Src access not defined
  22. 2013 Medium

    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

    PMID:23481397

    Open questions at the time
    • Molecular basis for integrin exclusion not resolved
    • Single-lab study
  23. 2016 Medium

    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

    PMID:27516388

    Open questions at the time
    • Downstream effectors of S268 phosphorylation not mapped
    • Single-lab study
  24. 2017 High

    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

    PMID:29078376

    Open questions at the time
    • Structural consequence of K547 ubiquitination on Rac1 regulation unknown
  25. 2019 High

    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

    PMID:30853440

    Open questions at the time
    • Molecular link between p120ctn dosage and sorting strength not fully resolved
  26. 2020 High

    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

    PMID:32741376

    Open questions at the time
    • Direct vs. cadherin-stability-dependent contribution to Shroom3 localization unclear
  27. 2022 High

    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

    PMID:35700046

    Open questions at the time
    • Mechanism by which p120ctn shields β-catenin from the destruction complex not structurally defined
  28. 2024 Medium

    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

    PMID:39179789

    Open questions at the time
    • Which specific isoform drives the rescue not pinpointed

Open questions

Synthesis pass · forward-looking unresolved questions
  • 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.
  • 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

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0098631 cell adhesion mediator activity 3 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 4 GO:0005886 plasma membrane 4 GO:0005829 cytosol 3 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1500931 Cell-Cell communication 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ARVCFCDH1CDH2CTNNB1GNA12MIB1PTPRMZBTB33
Complex memberships
cadherin-catenin complex (adherens junction)

Evidence

Reading pass · 38 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 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. Co-immunoprecipitation, immunofluorescence colocalization, immunoblotting in MDCK cells Molecular and cellular biology High 7526156
1995 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. Yeast two-hybrid, cell line analysis (PC3, SW480, HCT116) Molecular and cellular biology High 7651399
1996 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. Co-immunoprecipitation, transfection of CAS mutants in MDCK and NIH3T3 cells, immunofluorescence Experimental cell research Medium 8660921
1998 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. Affinity purification of proteins binding juxtamembrane region, deletion mutant analysis, laminar flow detachment assays, aggregation assays in Xenopus C-cadherin system The Journal of cell biology High 9566976
1998 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. cDNA cloning, exon mapping, RT-PCR isoform analysis Genomics Medium 9653641
1999 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. Yeast two-hybrid screen, monoclonal antibody co-immunoprecipitation, immunolocalization in mammalian cells Molecular and cellular biology High 10207085
1999 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. Deletion construct transfection, co-immunoprecipitation, aggregation assays, kinase inhibitor (staurosporine) treatment The Journal of biological chemistry Medium 10409703
1999 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. Overexpression of isoforms, microinjection of NES-carrier fusion proteins, leptomycin B treatment, immunofluorescence in multiple carcinoma cell lines Proceedings of the National Academy of Sciences of the United States of America High 10393933
2000 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. Stable transfection into E-cadherin-deficient cell lines, aggregation assays, detergent-free subcellular fractionation, actin cytoskeleton immunofluorescence The Journal of cell biology High 10629228
2000 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. Co-immunoprecipitation, in vitro dephosphorylation assay, mutational analysis, cell-based phosphorylation assay The Journal of biological chemistry High 10753936
2000 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). Co-immunoprecipitation, ARVCF/p120 chimera transfection, immunofluorescence Journal of cell science Medium 10725230
2001 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. 2D tryptic phosphopeptide mapping, site-directed mutagenesis (Y→F), in vitro and in vivo Src kinase assays, co-immunoprecipitation with SHP-1 The Journal of biological chemistry High 11382764
2001 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. L cell stable transfection with E-cadherin constructs, v-Src expression, aggregation assays, Y217F point mutant analysis Journal of cell science Medium 11171320
2002 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. In vitro binding assay, co-immunoprecipitation from embryo lysates, genetic analysis of Rho1 and p120ctn mutants Development (Cambridge, England) Medium 12135916
2002 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. GST-fusion substrate-trapping pull-down, co-immunoprecipitation, immunofluorescence colocalization Oncogene Medium 12370829
2002 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. Transient transfection of isoform expression constructs into melanoma and keratinocyte cells, immunofluorescence, nuclear localization analysis Journal of cell science Medium 11896187
2003 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. Cycloheximide chase, temperature block, immunofluorescence in polarized MDCK cells, E-cadherin deletion mutant (EcadΔS1) analysis The Journal of biological chemistry Medium 12923199
2004 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. siRNA-mediated knockdown, immunoblotting for cadherin levels Seminars in cell & developmental biology Medium 15561585
2004 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. NLS mutagenesis (K→A), heterologous NLS-GFP fusion protein nuclear import assay, minimal promoter transcriptional assays Journal of cell science High 15138284
2004 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. RNAi knockdown, Rho-GTPase activity assays, morphology and migration analysis The American journal of pathology Medium 15161659
2004 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. 5-azacytidine E-cadherin re-expression, stable transfection of transcriptional repressors, immunofluorescence Oncogene Medium 15077190
2005 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. Chromatin immunoprecipitation, minimal promoter transcription assays, RNAi depletion of Kaiso, KBS mutation, p120ctn NLS mutant Experimental cell research High 15817151
2005 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. Cell-free endocytosis assay, co-immunoprecipitation, dominant-negative afadin mutant analysis The Journal of biological chemistry Medium 15857834
2006 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. Stable transfection, co-immunoprecipitation, cadherin turnover assays, clathrin-dependent endocytosis inhibition Oncogene Medium 16786001
2004 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. Co-immunoprecipitation, in vitro binding, cell morphology analysis in multiple cell types, Rho activity assay Proceedings of the National Academy of Sciences of the United States of America Medium 15240885
2007 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. Overexpression of p120ctn 3A, confocal microscopy, co-immunoprecipitation with cyclin E/CDK2, synchronized cell cycle analysis, immunoblotting Cancer research Medium 17942908
2009 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. Co-immunoprecipitation, RhoA activity assays, Matrigel invasion assays in melanoma cells expressing E-cadherin The Journal of biological chemistry Medium 19293150
2010 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. Domain mapping with deletion mutants, co-immunoprecipitation, Src kinase phosphorylation assay, RhoA dominant-active mutant analysis Experimental cell research Medium 20974127
2013 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. FRET biosensors on micropatterned fibronectin strips, siRNA knockdown, fluorescence imaging in live cells Nature communications Medium 23481397
2016 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. Phosphorylation site analysis in TSC patient tubers, mTOR inhibitor treatment (Torin1), PKCε activity assays, cell adhesion assays Human molecular genetics Medium 27516388
2017 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. Ubiquitination assay identifying K547 site, Rac1 activation assay, wound-closure migration assay in HeLa cells, zebrafish genetic epistasis Proceedings of the National Academy of Sciences of the United States of America High 29078376
2019 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. Conditional mouse knockout, CRISPR/Cas9 in Xenopus, lineage tracing, cell sorting assays Developmental cell High 30853440
2020 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. Conditional knockout mice (p120ctnfl/fl;Del-Cre and p120ctnfl/fl;Wnt1-Cre), rescue by ROSA26-p120ctn in ES cells, immunofluorescence BMC developmental biology High 32741376
2022 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. Inducible endothelial-specific Ctnnd1 knockout mice, unbiased proteomics, GSK3β inhibitor treatment (LiCl, CHIR-99021), retinal vascular phenotype analysis, double-heterozygous genetic interaction JCI insight High 35700046
1999 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). Yeast two-hybrid, in vitro protein-protein interaction assay Journal of cellular biochemistry Medium 10321838
2001 MUC1 cytoplasmic domain binds directly to p120ctn and induces nuclear localization of p120ctn, providing a membrane-to-nucleus signaling pathway. Co-immunoprecipitation, direct binding assay, immunofluorescence nuclear localization analysis Biochemical and biophysical research communications Medium 11181067
2024 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. Zebrafish esrp1/2 mutant rescue by ctnnd1 overexpression, alternative splicing analysis, CRISPR/mutagenesis Communications biology Medium 39179789
2021 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. Immunoblotting, Rac1/Cdc42/PAK1/ERK activity assays, siRNA knockdown, MTT viability assay in HCC827 and PC9 cells Applied immunohistochemistry & molecular morphology Medium 34412070

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn. The Journal of cell biology 463 9566976
1994 Identification of a new catenin: the tyrosine kinase substrate p120cas associates with E-cadherin complexes. Molecular and cellular biology 431 7526156
2000 Selective uncoupling of p120(ctn) from E-cadherin disrupts strong adhesion. The Journal of cell biology 397 10629228
1999 The catenin p120(ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Molecular and cellular biology 346 10207085
1995 The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin. Molecular and cellular biology 199 7651399
1999 p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells. The Journal of cell biology 194 10225956
2002 Rho1 interacts with p120ctn and alpha-catenin, and regulates cadherin-based adherens junction components in Drosophila. Development (Cambridge, England) 160 12135916
2004 Cytoplasmic localization of p120ctn and E-cadherin loss characterize lobular breast carcinoma from preinvasive to metastatic lesions. Oncogene 152 15077190
1999 p120(ctn) binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity. The Journal of biological chemistry 152 10409703
2006 p120-ctn: A nexus for contextual signaling via Rho GTPases. Biochimica et biophysica acta 150 17028013
2005 Overexpressed P-cadherin/CDH3 promotes motility of pancreatic cancer cells by interacting with p120ctn and activating rho-family GTPases. Cancer research 148 15833838
1998 Molecular cloning of the human p120ctn catenin gene (CTNND1): expression of multiple alternatively spliced isoforms. Genomics 141 9653641
2005 Regulation of E-cadherin endocytosis by nectin through afadin, Rap1, and p120ctn. The Journal of biological chemistry 137 15857834
1999 Nuclear localization of the p120(ctn) Armadillo-like catenin is counteracted by a nuclear export signal and by E-cadherin expression. Proceedings of the National Academy of Sciences of the United States of America 136 10393933
1996 The novel catenin p120cas binds classical cadherins and induces an unusual morphological phenotype in NIH3T3 fibroblasts. Experimental cell research 131 8660921
2001 Identification of Src phosphorylation sites in the catenin p120ctn. The Journal of biological chemistry 126 11382764
2003 Abnormalities of E- and P-cadherin and catenin (beta-, gamma-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. The Journal of pathology 112 12635138
1996 Identification of murine p120 isoforms and heterogeneous expression of p120cas isoforms in human tumor cell lines. Cancer research 112 8653709
2000 Receptor protein-tyrosine phosphatase RPTPmu binds to and dephosphorylates the catenin p120(ctn). The Journal of biological chemistry 108 10753936
2005 A role for Kaiso-p120ctn complexes in cancer? Nature reviews. Cancer 103 16294216
2005 The catenin p120ctn inhibits Kaiso-mediated transcriptional repression of the beta-catenin/TCF target gene matrilysin. Experimental cell research 101 15817151
2006 Dancing in and out of the nucleus: p120(ctn) and the transcription factor Kaiso. Biochimica et biophysica acta 97 17050009
2004 Regulation of cadherin stability and turnover by p120ctn: implications in disease and cancer. Seminars in cell & developmental biology 97 15561585
2004 NLS-dependent nuclear localization of p120ctn is necessary to relieve Kaiso-mediated transcriptional repression. Journal of cell science 89 15138284
2005 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. Human pathology 77 16226102
2000 ARVCF localizes to the nucleus and adherens junction and is mutually exclusive with p120(ctn) in E-cadherin complexes. Journal of cell science 77 10725230
1998 The expression of p120ctn protein in breast cancer is independent of alpha- and beta-catenin and E-cadherin. The American journal of pathology 77 9422525
2004 Cytoplasmic p120ctn regulates the invasive phenotypes of E-cadherin-deficient breast cancer. The American journal of pathology 74 15161659
2001 Tyrosine phosphorylation of p120(ctn) in v-Src transfected L cells depends on its association with E-cadherin and reduces adhesion activity. Journal of cell science 74 11171320
2002 The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120(ctn). Oncogene 71 12370829
2004 E- and N-cadherin differ with respect to their associated p120ctn isoforms and their ability to suppress invasive growth in pancreatic cancer cells. Oncogene 67 15107817
2002 Specific sequences in p120ctn determine subcellular distribution of its multiple isoforms involved in cellular adhesion of normal and malignant epithelial cells. Journal of cell science 66 11896187
2001 Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. Human pathology 66 11521230
2006 Diverse functions of p120ctn in tumors. Biochimica et biophysica acta 62 17030444
2016 Overexpression of CTNND1 in hepatocellular carcinoma promotes carcinous characters through activation of Wnt/β-catenin signaling. Journal of experimental & clinical cancer research : CR 60 27193094
2020 Melatonin promotes cardiomyocyte proliferation and heart repair in mice with myocardial infarction via miR-143-3p/Yap/Ctnnd1 signaling pathway. Acta pharmacologica Sinica 56 32839503
2017 Blepharocheilodontic syndrome is a CDH1 pathway-related disorder due to mutations in CDH1 and CTNND1. Genetics in medicine : official journal of the American College of Medical Genetics 56 28301459
2001 The Human DF3/MUC1 carcinoma-associated antigen signals nuclear localization of the catenin p120(ctn). Biochemical and biophysical research communications 55 11181067
2003 Contextual binding of p120ctn to E-cadherin at the basolateral plasma membrane in polarized epithelia. The Journal of biological chemistry 53 12923199
2007 Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human gastric epithelial cells. Pathology, research and practice 52 17509776
2009 Overexpression of E-cadherin on melanoma cells inhibits chemokine-promoted invasion involving p190RhoGAP/p120ctn-dependent inactivation of RhoA. The Journal of biological chemistry 51 19293150
1998 Production and characterization of monoclonal antibodies to the catenin p120ctn. Hybridoma 50 9627058
2006 Expression of inappropriate cadherins by epithelial tumor cells promotes endocytosis and degradation of E-cadherin via competition for p120(ctn). Oncogene 49 16786001
2019 Hsa_circ_0002577 promotes endometrial carcinoma progression via regulating miR-197/CTNND1 axis and activating Wnt/β-catenin pathway. Cell cycle (Georgetown, Tex.) 48 31081718
2018 Variants in members of the cadherin-catenin complex, CDH1 and CTNND1, cause blepharocheilodontic syndrome. European journal of human genetics : EJHG 46 29348693
2012 Functions of p120ctn isoforms in cell-cell adhesion and intracellular signaling. Frontiers in bioscience (Landmark edition) 46 22201829
2013 N-cadherin regulates spatially polarized signals through distinct p120ctn and β-catenin-dependent signalling pathways. Nature communications 44 23481397
2000 The catenin, p120ctn, is a common membrane-associated protein in various epithelial and non-epithelial cells and tissues. Histochemistry and cell biology 44 11052263
2010 delta-Catenin promotes malignant phenotype of non-small cell lung cancer by non-competitive binding to E-cadherin with p120ctn in cytoplasm. The Journal of pathology 41 20593408
2005 Rho1 regulates Drosophila adherens junctions independently of p120ctn. Development (Cambridge, England) 41 16207756
2019 SNHG29 regulates miR-223-3p/CTNND1 axis to promote glioblastoma progression via Wnt/β-catenin signaling pathway. Cancer cell international 38 31889897
2022 CTNND1 variants cause familial exudative vitreoretinopathy through the Wnt/cadherin axis. JCI insight 36 35700046
2010 Gene amplification of the transcription factor DP1 and CTNND1 in human lung cancer. The Journal of pathology 36 20556744
2010 p120ctn and P-cadherin but not E-cadherin regulate cell motility and invasion of DU145 prostate cancer cells. PloS one 35 20668551
2001 Tissue distribution and cell type-specific expression of p120ctn isoforms. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 34 11724896
2007 Cyclin-dependent kinase 2/cyclin E complex is involved in p120 catenin (p120ctn)-dependent cell growth control: a new role for p120ctn in cancer. Cancer research 33 17942908
2020 The circular RNA circMAST1 promotes hepatocellular carcinoma cell proliferation and migration by sponging miR-1299 and regulating CTNND1 expression. Cell death & disease 31 32393764
2020 Hsa-miR-425-5p promotes tumor growth and metastasis by activating the CTNND1-mediated β-catenin pathway and EMT in colorectal cancer. Cell cycle (Georgetown, Tex.) 31 32594834
2017 Chromatin remodeling protein MORC2 promotes breast cancer invasion and metastasis through a PRD domain-mediated interaction with CTNND1. Oncotarget 31 29228664
2008 Nuclear targeting of beta-catenin and p120ctn during thrombin-induced endothelial barrier dysfunction. Cardiovascular research 31 18490349
1999 Up-regulated cytoplasmic expression, with reduced membranous distribution, of the src substrate p120(ctn) in gastric carcinoma. The Journal of pathology 30 10547572
2020 Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome. Human molecular genetics 29 32196547
2006 E-cadherin regulates human Nanos1, which interacts with p120ctn and induces tumor cell migration and invasion. Cancer research 29 17047063
2021 Silencing CTNND1 Mediates Triple-Negative Breast Cancer Bone Metastasis via Upregulating CXCR4/CXCL12 Axis and Neutrophils Infiltration in Bone. Cancers 28 34830862
2019 p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate. Developmental cell 26 30853440
2002 An octapeptide in the juxtamembrane domain of VE-cadherin is important for p120ctn binding and cell proliferation. Experimental cell research 26 11855855
2018 RETRACTED: MicroRNA-298 represses hepatocellular carcinoma progression by inhibiting CTNND1-mediated Wnt/β-catenin signaling. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 25 29990836
2007 Reduction of p120(ctn) isoforms 1 and 3 is significantly associated with metastatic progression of human lung cancer. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica 25 17614852
2005 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. Genes to cells : devoted to molecular & cellular mechanisms 25 15836772
2020 MicroRNA-96-5p represses breast cancer proliferation and invasion through Wnt/β-catenin signaling via targeting CTNND1. Scientific reports 24 31913290
2017 Mib1 contributes to persistent directional cell migration by regulating the Ctnnd1-Rac1 pathway. Proceedings of the National Academy of Sciences of the United States of America 24 29078376
1999 Human p120ctn catenin: tissue-specific expression of isoforms and molecular interactions with BP180/type XVII collagen. Journal of cellular biochemistry 24 10321838
2009 Kaiso is expressed in lung cancer: its expression and localization is affected by p120ctn. Lung cancer (Amsterdam, Netherlands) 23 19615783
1996 The gene encoding p120cas, a novel catenin, localizes on human chromosome 11q11 (CTNND) and mouse chromosome 2 (Catns). Genomics 21 8808291
2020 Circular RNA circ_0000043 promotes endometrial carcinoma progression by regulating miR-1271-5p/CTNND1 axis. Archives of gynecology and obstetrics 20 33128584
2001 Monoclonal antibodies to Kaiso: a novel transcription factor and p120ctn-binding protein. Hybridoma 20 11461664
1999 Expression of catenins and p120cas in melanocytic nevi and cutaneous melanoma: deficient alpha-catenin expression is associated with melanoma progression. Pathology 20 10503270
2014 Glial cell-derived neurotrophic factor attenuates neuropathic pain in a mouse model of chronic constriction injury: possible involvement of E-cadherin/p120ctn signaling. Journal of molecular neuroscience : MN 19 24599758
2004 A role for Galpha12/Galpha13 in p120ctn regulation. Proceedings of the National Academy of Sciences of the United States of America 18 15240885
1999 Expression patterns of the novel catenin p120cas in gastrointestinal cancers. Anticancer research 18 10650783
2000 Regulation of adherens junction protein p120(ctn) by 10 nM CCK precedes actin breakdown in rat pancreatic acini. American journal of physiology. Gastrointestinal and liver physiology 17 10712269
2020 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. Cancer cell international 16 32760218
2001 alpha-, beta-, gamma-catenin, and p120(CTN) expression during the terminal differentiation and fusion of human mononucleate cytotrophoblasts in vitro and in vivo. Molecular reproduction and development 15 11389551
2018 Jinfu'an Decoction Inhibits Invasion and Metastasis in Human Lung Cancer Cells (H1650) via p120ctn-Mediated Induction and Kaiso. Medical science monitor : international medical journal of experimental and clinical research 13 29735970
2015 Expressions of E-cadherin, p120ctn, β-catenin and NF-κB in ulcerative colitis. 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 12 26072075
2016 Catenin delta-1 (CTNND1) phosphorylation controls the mesenchymal to epithelial transition in astrocytic tumors. Human molecular genetics 11 27516388
2013 Heme oxygenase-1 promotes Caco-2 cell proliferation and migration by targeting CTNND1. Chinese medical journal 11 23981612
2021 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. PloS one 10 34784403
2024 CTNND1 is involved in germline predisposition to early-onset gastric cancer by affecting cell-to-cell interactions. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 9 38796558
2016 Increasing diagnostic accuracy to grade dysplasia in Barrett's esophagus using an immunohistochemical panel for CDX2, p120ctn, c-Myc and Jagged1. Diagnostic pathology 9 26926447
2015 C6orf106 enhances NSCLC cell invasion by upregulating vimentin, and downregulating E-cadherin and P120ctn. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 9 25736925
2024 Functional analysis of ESRP1/2 gene variants and CTNND1 isoforms in orofacial cleft pathogenesis. Communications biology 8 39179789
2007 Expression of E-cadherin, beta-catenin and p120ctn in the pulmonary sclerosing hemangioma. Lung cancer (Amsterdam, Netherlands) 8 17383052
2024 EIF4A3-negatively driven circular RNA β-catenin (circβ-catenin) promotes colorectal cancer progression via miR-197-3p/CTNND1 regulatory axis. British journal of cancer 7 38459187
2021 Cytoplasmic P120ctn Promotes Gefitinib Resistance in Lung Cancer Cells by Activating PAK1 and ERK Pathway. Applied immunohistochemistry & molecular morphology : AIMM 7 34412070
2020 Neural defects caused by total and Wnt1-Cre mediated ablation of p120ctn in mice. BMC developmental biology 7 32741376
2006 P120ctn overexpression enhances beta-catenin-E-cadherin binding and down regulates expression of survivin and cyclin D1 in BEL-7404 hepatoma cells. World journal of gastroenterology 7 16534869
2023 Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer. Cancers 6 37686589
2016 P120ctn may participate in epithelial-mesenchymal transition in OSCC. Indian journal of cancer 6 27146732
2010 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. Experimental cell research 6 20974127

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