Affinage

CTNNB1

Catenin beta-1 · UniProt P35222

Round 2 corrected
Length
781 aa
Mass
85.5 kDa
Annotated
2026-04-28
130 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTNNB1 (beta-catenin) is a dual-function armadillo-repeat scaffold protein that serves as both a structural component of adherens junctions and the central transcriptional effector of the canonical Wnt signaling pathway. At cell-cell junctions, beta-catenin bridges E-cadherin to alpha-catenin and the actin cytoskeleton, and its loss abolishes epithelial cell adhesion and polarity (PMID:1962194, PMID:8698810, PMID:8943306). In the Wnt-OFF state, CKIalpha-primed and GSK3beta-phosphorylated beta-catenin is ubiquitinated by SCF(beta-TrCP) within an intact Axin/APC destruction complex that also requires YAP/TAZ for beta-TrCP recruitment; Wnt signaling blocks ubiquitination (not phosphorylation) within this complex, allowing newly synthesized beta-catenin to accumulate, translocate to the nucleus, and co-activate TCF/LEF target genes—a process modulated by AKT phosphorylation at Ser552, CK2 phosphorylation at Thr393, deubiquitinases UCHL3 and JOSD2, selective TRAF6/LC3B-mediated autophagy, and the nuclear co-factor BCL9/Legless (PMID:11955436, PMID:22682247, PMID:24976009, PMID:9990852, PMID:17287208, PMID:12700239, PMID:30806153, PMID:15294866). Truncating CTNNB1 variants cause familial exudative vitreoretinopathy (FEVR) through loss of Norrin/beta-catenin signaling in retinal endothelium (PMID:35361685).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1990 High

    Establishing that Armadillo (beta-catenin ortholog) protein levels are post-transcriptionally regulated by Wingless signaling answered the foundational question of how a segment-polarity gene product is controlled by the Wnt ligand.

    Evidence Genetic epistasis and immunostaining in Drosophila embryos

    PMID:2225066

    Open questions at the time
    • Mechanism of Wingless-dependent stabilization unknown
    • Vertebrate homolog not yet identified
  2. 1991 High

    Identification of beta-catenin as the Armadillo homolog and component of the cadherin–catenin complex established its molecular identity and junction-associated role, unifying adhesion and signaling functions under one gene.

    Evidence cDNA cloning, sequence homology, monoclonal antibody localization in MDCK cells

    PMID:1962194

    Open questions at the time
    • Direct demonstration of alpha-catenin binding domain not yet mapped
    • Signaling function in vertebrates not yet shown
  3. 1996 High

    Mapping of distinct binding domains for alpha-catenin, cadherin, and the new partner LEF-1, combined with the demonstration that beta-catenin–LEF-1 enters the nucleus and induces axis duplication, resolved how a junctional protein could simultaneously serve as a transcriptional co-activator.

    Evidence Yeast two-hybrid, in vitro binding, co-IP, microinjection in Xenopus embryos; mutant allele analysis in Drosophila

    PMID:8638126 PMID:8698810 PMID:8757136 PMID:8943306

    Open questions at the time
    • Structural basis of multi-partner binding unresolved
    • Mechanism of GSK3beta-dependent degradation incomplete
  4. 1997 High

    Demonstration that APC or beta-catenin mutations in colorectal tumors constitutively activate beta-catenin/Tcf-4 transcription, and that the armadillo repeat domain forms a positively charged superhelical groove, linked the destruction-complex pathway to cancer and provided the first structural framework for multi-partner recognition.

    Evidence Tcf reporter assays in tumor specimens; X-ray crystallography of armadillo repeat core; GSK3-dependent stability assays in Drosophila

    PMID:9065401 PMID:9065402 PMID:9187151 PMID:9298899

    Open questions at the time
    • Scaffold architecture of the destruction complex not defined
    • Identity of the E3 ligase unknown
  5. 1998 High

    Identification of Axin as the scaffold that directly bridges beta-catenin to GSK3beta and APC, dramatically facilitating phosphorylation, defined the quaternary destruction complex and explained how multiple tumor suppressors converge on beta-catenin turnover.

    Evidence Yeast two-hybrid, co-IP, in vitro kinase assays, overexpression in colon cancer cells

    PMID:9482734 PMID:9601641

    Open questions at the time
    • Priming kinase for GSK3beta phosphorylation unidentified
    • Ubiquitin ligase not yet linked
  6. 1999 High

    Discovery that SCF(beta-TrCP) recognizes a phosphorylated destruction motif on beta-catenin and catalyzes its ubiquitination completed the phosphorylation-to-degradation cascade and identified the E3 ligase.

    Evidence Biochemical fractionation, in vitro ubiquitination assay, phospho-peptide binding

    PMID:9990852

    Open questions at the time
    • Mechanism by which Wnt blocks degradation unknown
    • Role of additional kinases not explored
  7. 2002 High

    Identification of CKIalpha as the priming kinase required before GSK3beta phosphorylation resolved the long-standing question of how the destruction complex initiates beta-catenin phosphorylation and explained the sequential kinase mechanism.

    Evidence In vitro kinase assay, RNAi depletion in Xenopus embryos, protein stability assays

    PMID:11955436

    Open questions at the time
    • No structural view of CKIalpha–Axin–beta-catenin ternary complex
    • Wnt-mediated inhibition mechanism still not molecularly defined
  8. 2004 High

    Separation-of-function studies demonstrated that nuclear localization of beta-catenin is strictly required for transcriptional output, and that BCL9/Legless binds a distinct surface on the first armadillo repeat to recruit the Pygopus co-activator, refining the nuclear transcription complex architecture.

    Evidence Transgenic Drosophila mutant analysis; yeast two-hybrid and site-directed mutagenesis of ARM repeat 1

    PMID:15024404 PMID:15294866

    Open questions at the time
    • Mechanism of nuclear import/export not defined
    • Vertebrate BCL9 interaction surface not structurally resolved
  9. 2007 High

    AKT phosphorylation of beta-catenin at Ser552 was shown to dissociate it from junctions, promote nuclear accumulation via 14-3-3zeta binding, and enhance transcriptional activity, establishing a Wnt-independent signaling input onto beta-catenin.

    Evidence In vitro kinase assay, mass spectrometry, co-IP, nuclear fractionation

    PMID:17287208

    Open questions at the time
    • Physiological context of AKT-mediated regulation in normal tissue unclear
    • Interplay with destruction complex phosphorylation not addressed
  10. 2012 High

    The paradigm-shifting finding that Wnt blocks ubiquitination—not phosphorylation—of beta-catenin within an intact destruction complex, causing complex saturation and accumulation of newly synthesized beta-catenin, redefined the signal transduction mechanism.

    Evidence Endogenous complex biochemistry, mass spectrometry, in-complex ubiquitination assays in intestinal epithelium and CRC cells

    PMID:22682247

    Open questions at the time
    • Molecular mechanism by which Wnt inhibits ubiquitination within the complex unresolved
    • Stoichiometry of complex saturation not quantified
  11. 2014 High

    Discovery that YAP/TAZ are integral destruction-complex components required for beta-TrCP recruitment to beta-catenin in Wnt-OFF cells, and are released upon Wnt activation, established a direct mechanistic link between Wnt and Hippo signaling pathways.

    Evidence Reciprocal co-IP, genetic knockdown/knockout, epistasis in APC-deficient intestinal organoids

    PMID:24976009

    Open questions at the time
    • Structural basis of YAP/TAZ–destruction complex interaction unknown
    • Whether YAP/TAZ release is the cause or consequence of beta-catenin accumulation not fully resolved
  12. 2019 High

    Identification of TRAF6-mediated K63-linked polyubiquitination of LC3B as a trigger for selective autophagic degradation of beta-catenin, counter-regulated by GSK3B phosphorylation of TRAF6, revealed an autophagy-based parallel degradation route independent of the proteasome.

    Evidence Ubiquitin chain-type-specific pulldown, LC3B–ATG7 complex assay, GSK3B kinase assay, autophagy flux assays

    PMID:30806153

    Open questions at the time
    • Relative quantitative contribution of autophagy versus proteasomal degradation in vivo unknown
    • Tissue-specific relevance not established
  13. 2022 High

    Truncating CTNNB1 variants were shown to cause familial exudative vitreoretinopathy (FEVR) through loss of Norrin/beta-catenin signaling, connecting haploinsufficiency of CTNNB1 to a Mendelian vascular disease.

    Evidence Dual-luciferase reporter, siRNA knockdown in retinal endothelial cells, conditional heterozygous knockout mice with FEVR phenotype rescued by LiCl

    PMID:35361685

    Open questions at the time
    • Penetrance and genotype–phenotype spectrum across different CTNNB1 variants not characterized
    • Whether other vascular beds are affected is unexplored

Open questions

Synthesis pass · forward-looking unresolved questions
  • The precise molecular mechanism by which Wnt-activated receptors inhibit beta-catenin ubiquitination within the intact destruction complex remains undefined, as does the structural basis for how the C-terminal domain shields the armadillo repeats from Axin association.
  • No reconstituted system demonstrates Wnt-receptor-to-ubiquitination-block mechanism
  • High-resolution structure of full-length beta-catenin within the destruction complex unavailable
  • Quantitative contribution of selective autophagy versus proteasomal degradation in different tissues unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0008092 cytoskeletal protein binding 4 GO:0005198 structural molecule activity 3 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 6 GO:0005634 nucleus 5 GO:0005829 cytosol 4 GO:0005856 cytoskeleton 3
Pathway
R-HSA-162582 Signal Transduction 12 R-HSA-1266738 Developmental Biology 4 R-HSA-1500931 Cell-Cell communication 4 R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 1 R-HSA-9612973 Autophagy 1
Partners
APCAXIN1BCL9CSNK1A1GSK3BLEF1TCF7L2YAP1
Complex memberships
Axin/APC/GSK3beta destruction complexBeta-catenin–TCF/LEF transcription complexCadherin–catenin adhesion complex

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Beta-catenin (the 92-kDa catenin of Xenopus laevis) is homologous to mammalian plakoglobin and Drosophila Armadillo, and binds to the cytoplasmic tail of E-cadherin as part of a catenin complex that links E-cadherin to the actin cytoskeleton at cell-cell junctions. cDNA cloning, sequence analysis, monoclonal antibody recognition in MDCK cells Science High 1962194
1990 Drosophila Armadillo (beta-catenin ortholog) protein accumulates post-transcriptionally in regions of Wingless signaling; Wingless regulates Armadillo protein levels, and Armadillo associates with the plasma membrane and co-localizes with F-actin. Genetic epistasis, protein localization by immunostaining in Drosophila embryos Cell High 2225066
1996 Armadillo (Drosophila beta-catenin) is essential for adherens junction assembly in vivo; loss of Armadillo abolishes cell-cell adhesion, causes loss of epithelial cell polarity, and blocks gastrulation morphogenesis. Mutant allele analysis (armadilloXP33), immunostaining in Drosophila embryos Journal of Cell Biology High 8698810
1996 A 76-amino acid region of Drosophila Armadillo is necessary and sufficient for alpha-catenin binding, while six central Armadillo repeats are required for DE-cadherin binding; the N-terminal 258 amino acids of alpha-catenin interact with Armadillo. In vitro binding assays, yeast two-hybrid, in vivo assays in Drosophila Journal of Biological Chemistry High 8943306
1996 Beta-catenin directly interacts with the transcription factor LEF-1 in a yeast two-hybrid screen; co-expressed LEF-1 and beta-catenin form a nuclear complex in mammalian cells, form a ternary complex with DNA, and microinjection into Xenopus embryos induces axis duplication, providing a molecular mechanism for signal transmission to the nucleus. Yeast two-hybrid, co-immunoprecipitation, microinjection in Xenopus embryos Nature High 8757136
1996 GSK3beta binds to the APC-beta-catenin complex; APC is a good substrate for GSK3beta in vitro, and phosphorylation of APC by GSK3beta is required for APC to bind beta-catenin, revealing a phosphorylation-dependent mechanism regulating complex assembly. Co-immunoprecipitation, in vitro kinase assay with phosphorylation site mapping Science High 8638126
1997 Beta-catenin or APC mutations in colorectal tumors activate beta-catenin/Tcf-4-dependent transcription; APC downregulates beta-catenin-Tcf transcriptional activity, and APC mutations in colorectal tumors are defective in this activity; activating beta-catenin mutations alter phosphorylation sites critical for regulation. Tcf reporter transcription assay, mutational analysis of colorectal tumor specimens Science High 9065401 9065402
1997 Beta-catenin-hTcf-4 forms a constitutively active nuclear complex in APC-/- colon carcinoma cells that drives Tcf target gene transcription; reintroduction of APC removes beta-catenin from hTcf-4 and abrogates transcriptional activation. Tcf reporter transcription assay, nuclear complex detection, APC re-expression Science High 9065401
1997 The three-dimensional structure of the 12-armadillo-repeat core of beta-catenin forms a superhelix of helices with a long positively charged groove; the beta-catenin binding regions of cadherins, Tcfs, and APC are acidic and proposed to interact with this groove. X-ray crystallography of protease-resistant armadillo repeat fragment Cell High 9298899
1997 Drosophila Armadillo is negatively regulated by Zeste-white 3 (GSK3 homolog) kinase, which phosphorylates Armadillo and modulates its protein stability; a 54-amino-acid N-terminal deletion mutant (ArmS10) escapes this regulation, becomes more stable, accumulates outside junctions, and is constitutively active for Wingless signaling. Dominant mutant analysis, protein stability assays, genetic epistasis in Drosophila Development High 9187151
1998 Axin directly binds beta-catenin via its armadillo repeats, forms a ternary complex with GSK3beta and beta-catenin, and promotes GSK3beta-dependent phosphorylation of beta-catenin, acting as a scaffold that negatively regulates Wnt signaling. Yeast two-hybrid, co-immunoprecipitation, in vitro kinase assay EMBO Journal High 9482734
1998 Human Axin binds directly to beta-catenin, GSK3beta, and APC in vitro; all endogenous proteins form a complex in cells; Axin dramatically facilitates GSK3beta-dependent phosphorylation of APC and beta-catenin; overexpression of Axin promotes downregulation of wild-type but not oncogenic mutant beta-catenin in colon cancer cells. In vitro pulldown, co-immunoprecipitation, in vitro kinase assay, overexpression in colon cancer cells Current Biology High 9601641
1999 The SCFbeta-TRCP ubiquitin ligase complex specifically recognizes a phosphorylated destruction motif in beta-catenin analogous to that in IkappaBalpha, and stimulates phosphorylation-dependent ubiquitination of beta-catenin, linking its degradation to the proteasome pathway. Biochemical fractionation, in vitro ubiquitination assay, destruction motif peptide binding Genes & Development High 9990852
2001 Drosophila APC2 and Armadillo (beta-catenin ortholog) participate in tethering mitotic spindles to cortical actin during syncytial mitoses; APC2-Armadillo complexes co-localize with interphase microtubules and cortical spindle attachment sites; Zeste-white 3 kinase regulates this localization. Genetic analysis, immunolocalization in Drosophila embryos, live imaging Nature Cell Biology High 11584277
2002 Beta-catenin phosphorylation and degradation is initiated by a dual-kinase mechanism: CKIalpha first phosphorylates beta-catenin (priming), which is required for subsequent GSK-3 phosphorylation; depletion of CKIalpha inhibits beta-catenin phosphorylation and degradation, causing excessive Wnt/beta-catenin signaling. In vitro kinase assay, RNAi depletion in Xenopus embryos, protein stability assays Cell High 11955436
2003 CK2 phosphorylates beta-catenin primarily within its armadillo repeat domain at Thr393; mutation of Thr393 reduces beta-catenin phosphorylation, co-transcriptional activity, and stability; CK2 inhibition reduces beta-catenin levels via the proteasome, identifying CK2 as a positive regulator of Wnt signaling. In vitro kinase assay, phospho-site mutagenesis, CK2 inhibitor treatment, transcription reporter assay Journal of Biological Chemistry High 12700239
2004 Nuclear localization of beta-catenin is necessary for Wnt pathway activation; membrane-tethered beta-catenin is insufficient to activate transcription; two missense point mutations that retain protein stability but abolish nuclear function define signaling-null conditions; the C-terminus-specific regulator Chibby acts on nuclear beta-catenin. Transgenic analysis in Drosophila, truncation and missense mutant functional assays, genetic epistasis PLoS Biology High 15024404
2004 The Legless (BCL9 homolog) adaptor protein directly binds to two acidic residues in the first Armadillo repeat of beta-catenin at a site spatially and functionally separable from the TCF, APC, and E-cadherin binding sites; this interaction is required for Wingless signaling output and recruits the transcriptional activator Pygopus. Yeast two-hybrid, site-directed mutagenesis, genetic assays in Drosophila Development High 15294866
2004 Drosophila PP2A regulatory subunit Twins (B/PR55) positively regulates Wingless signaling by stabilizing Armadillo/beta-catenin; it functions downstream of Dishevelled and upstream of Sgg (GSK3) and Armadillo as established by genetic epistasis. Genetic epistasis, mitotic clone analysis in Drosophila wing discs Development Medium 14973271
2007 AKT phosphorylates beta-catenin at Ser552 in vitro and in vivo; this phosphorylation causes dissociation of beta-catenin from cell-cell contacts, accumulation in cytosol and nucleus, enhanced interaction with 14-3-3zeta, increased transcriptional activity, and promotion of tumor cell invasion. In vitro kinase assay, mass spectrometry phospho-site identification, co-immunoprecipitation, nuclear fractionation Journal of Biological Chemistry High 17287208
2009 The unstructured C-terminal domain (CTD) of beta-catenin shields the armadillo repeat region from the axin-scaffold destruction complex; forms of beta-catenin lacking the CTD show enhanced axin association and faster turnover; FRET analysis shows the CTD can adopt an N-terminal orientation close to the armadillo repeats, and this orientation is required for stability. Co-transfection binding assay, in vitro competitive binding, FRET (CFP-arm-CTD-YFP), protein stability assay Journal of Biological Chemistry High 19706613
2009 The caspase DrICE cleaves Drosophila Armadillo at a DQVD motif in the N-terminal domain during apoptosis; this creates a stable membrane-associated fragment and is required for removal of DE-cadherin from the plasma membrane during apoptosis; mutation of the cleavage site prevents cleavage in vitro and in vivo. In vitro caspase cleavage assay, mutagenesis, immunostaining in Drosophila embryos BMC Developmental Biology Medium 19232093
2011 Nuclear PKM2 binds to c-Src-phosphorylated Y333 of beta-catenin; this interaction recruits both proteins to the CCND1 promoter, causes HDAC3 removal, histone H3 acetylation, and cyclin D1 expression, driving tumor cell proliferation upon EGFR activation. Co-immunoprecipitation, ChIP assay, EGFR activation/inhibition, nuclear fractionation, mutagenesis of phospho-site Nature High 22056988
2012 Wnt signaling does not disassemble the Axin1 destruction complex or inhibit phosphorylation of Axin1-bound beta-catenin; instead, it suppresses beta-catenin ubiquitination within an intact complex, causing complex saturation by phospho-beta-catenin, after which newly synthesized beta-catenin accumulates in free cytosolic form and engages nuclear TCF transcription factors. Endogenous protein complex analysis, mass spectrometry, in-complex ubiquitination assay, Wnt stimulation in intestinal epithelium and CRC cells Cell High 22682247
2012 CTNNB1 (beta-catenin) activation in Sertoli cells induces WNT4 expression; WNT4 acts as a paracrine factor that depletes spermatogonial stem cell activity; conditional deletion of Wnt4 in the CTNNB1-activated model rescues spermatogenesis, establishing a CTNNB1→WNT4 axis in the stem cell niche. Conditional transgenic/knockout mice, SSC transplant assay, microarray, WNT4 treatment of germ cell cultures PLoS One High 22253774
2014 YAP and TAZ are integral components of the beta-catenin destruction complex serving as a cytoplasmic sink; upon Wnt activation, YAP/TAZ are physically dislodged from the complex, enabling both their nuclear accumulation and beta-catenin signaling; in Wnt-OFF cells, YAP/TAZ are required for beta-TrCP recruitment and beta-catenin inactivation. Co-immunoprecipitation, genetic knockdown/knockout, epistasis in APC-deficient intestinal organoids Cell High 24976009
2014 Kinesin-II subunit Klp64D (Drosophila Kif3A homolog) directly binds to the armadillo repeat domain of Armadillo and recruits Dishevelled; klp64D mutants cause abnormal vesicular accumulation of Armadillo in Golgi, impairing intracellular trafficking of Armadillo required for Wingless signaling; human KIF3A rescues klp64D knockdown phenotypes and also binds beta-catenin. Genetic epistasis in Drosophila, direct binding assay, immunolocalization, rescue with human KIF3A Development Medium 25063455
2014 Endocytosis inhibitors reduce the basal pool of beta-catenin upon which GSK3beta acts, thereby preventing Wnt/Wingless signaling downstream of the ligand-receptor complex; LRP6/Arrow does not traffic to MVBs in Drosophila cells or wing discs, and MVBs are not required for Wnt signaling. Chemical inhibition (Dynasore, Dyngo-4a), epistasis with GSK3beta inhibitors, genetic knockdown in Drosophila cells and wing discs Journal of Cell Science Medium 25236598
2015 Muscle Ctnnb1 (beta-catenin) transcriptional activity (not cell-adhesion function) is required for presynaptic differentiation at the neuromuscular junction; Slit2 is identified as a beta-catenin-directed retrograde factor from muscle; Slit2 expressed in muscle rescues presynaptic deficits of Ctnnb1 mutation, and Slit2-coated beads induce synaptophysin puncta in axons. In vivo transgenic complementation, muscle-specific expression of Slit2, bead-induced synaptogenesis assay in spinal cord explants eLife High 26159615
2016 CTNNB1 deletion specifically in parvalbumin interneurons increases anxiety, impairs object recognition and social interactions, elevates repetitive behaviors, and enhances spatial memory; c-Fos is reduced in the cortex, revealing a cell-type-specific role of CTNNB1 in regulating inhibitory circuitry and ASD-related behaviors. Conditional knockout mice (PV-Cre), behavioral battery, c-Fos immunostaining Human Molecular Genetics High 27131348
2019 TRAF6 drives selective autophagic degradation of CTNNB1 by catalyzing K63-linked polyubiquitination of LC3B via its LIR motif, promoting LC3B-ATG7 complex formation and subsequent CTNNB1 recognition by LC3B; GSK3B phosphorylates TRAF6 at Thr266, triggering K48-linked ubiquitination and TRAF6 degradation, thereby attenuating autophagic CTNNB1 clearance. Co-immunoprecipitation, ubiquitin chain-type specific pulldown, LC3B-ATG7 complex assay, GSK3B kinase assay, autophagy flux assays Autophagy High 30806153
2019 ACLY interacts with CTNNB1 protein and stabilizes it; the ACLY-CTNNB1 complex promotes CTNNB1 translocation from cytoplasm to nucleus, enhancing CTNNB1 transcriptional activity and colon cancer cell migration and invasion. Co-immunoprecipitation, Western blot, nuclear/cytoplasmic fractionation, migration/invasion assays in ACLY-deficient cells Journal of Experimental & Clinical Cancer Research Medium 31511060
2021 UCHL3 deubiquitinase binds to CTNNB1 and decreases its ubiquitination level, stabilizing CTNNB1 protein and activating the Wnt signaling pathway; UCHL3 function depends on its deubiquitination activity. Co-immunoprecipitation, ubiquitination assay, CRISPR-Cas9 knockout, dual-luciferase reporter, xenograft model Journal of Translational Medicine Medium 37740194
2022 JOSD2 deubiquitinase binds to CTNNB1 and decreases its ubiquitination, thereby stabilizing CTNNB1 and augmenting Wnt pathway transduction in hepatocellular carcinoma. Co-immunoprecipitation, ubiquitination assay, RNA-seq, rescue experiments Cell Biology International Medium 35568970
2024 GSTA1 forms a cytoplasmic complex with CTNNB1 that facilitates nuclear translocation of CTNNB1, establishing a positive feedback loop; CTNNB1 transcriptionally upregulates GSTA1; the GSTA1/CTNNB1 axis suppresses ferroptosis and mediates sorafenib resistance in hepatocellular carcinoma. Co-immunoprecipitation, nuclear translocation assay, ChIP-like transcriptional analysis, CRISPR knockout, organoids, xenograft Pharmacological Research Medium 39510148
2022 Truncating CTNNB1 variants cause loss of Norrin/beta-catenin signaling activity; CTNNB1 knockdown in human retinal microvascular endothelial cells reduces Norrin/beta-catenin target gene expression, impairs cell proliferation, and compromises junctional integrity; heterozygous endothelial-specific Ctnnb1 knockout mice display FEVR-like retinal phenotypes rescued by LiCl. Dual-luciferase reporter, Western blot, co-immunoprecipitation, siRNA knockdown, transendothelial electrical resistance assay, conditional knockout mice Journal of Medical Genetics High 35361685

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science (New York, N.Y.) 3583 9065402
1997 Constitutive transcriptional activation by a beta-catenin-Tcf complex in APC-/- colon carcinoma. Science (New York, N.Y.) 2987 9065401
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1996 Functional interaction of beta-catenin with the transcription factor LEF-1. Nature 2587 8757136
2003 Epithelial-mesenchymal transition and its implications for fibrosis. The Journal of clinical investigation 2057 14679171
2013 Fusobacterium nucleatum promotes colorectal carcinogenesis by modulating E-cadherin/β-catenin signaling via its FadA adhesin. Cell host & microbe 1857 23954158
2002 Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 1758 11955436
2012 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins. Cell 1718 22658674
2017 Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer cell 1665 28810144
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1996 Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science (New York, N.Y.) 1275 8638126
2012 Diagnostic exome sequencing in persons with severe intellectual disability. The New England journal of medicine 1245 23033978
1993 Association of the APC tumor suppressor protein with catenins. Science (New York, N.Y.) 1142 8259519
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1998 Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. The EMBO journal 1086 9482734
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2000 Proteomic analysis of NMDA receptor-adhesion protein signaling complexes. Nature neuroscience 977 10862698
2012 Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nature genetics 958 22504420
2011 Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proceedings of the National Academy of Sciences of the United States of America 945 21949397
2011 Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 920 22056988
2014 YAP/TAZ incorporation in the β-catenin destruction complex orchestrates the Wnt response. Cell 916 24976009
2011 Yap1 acts downstream of α-catenin to control epidermal proliferation. Cell 893 21376238
2012 Intestinal tumorigenesis initiated by dedifferentiation and acquisition of stem-cell-like properties. Cell 873 23273993
1999 The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes & development 832 9990852
2018 VIRMA mediates preferential m6A mRNA methylation in 3'UTR and near stop codon and associates with alternative polyadenylation. Cell discovery 829 29507755
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2007 Phosphorylation of beta-catenin by AKT promotes beta-catenin transcriptional activity. The Journal of biological chemistry 748 17287208
1998 Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Current biology : CB 739 9601641
2012 Wnt signaling through inhibition of β-catenin degradation in an intact Axin1 complex. Cell 734 22682247
1991 A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin. Science (New York, N.Y.) 583 1962194
1997 Three-dimensional structure of the armadillo repeat region of beta-catenin. Cell 580 9298899
1990 Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by wingless. Cell 338 2225066
1996 Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis. The Journal of cell biology 271 8698810
1997 Negative regulation of Armadillo, a Wingless effector in Drosophila. Development (Cambridge, England) 260 9187151
2019 ACLY facilitates colon cancer cell metastasis by CTNNB1. Journal of experimental & clinical cancer research : CR 187 31511060
2017 Exon 3 mutations of CTNNB1 drive tumorigenesis: a review. Oncotarget 179 29435196
2019 m6A mRNA methylation regulates CTNNB1 to promote the proliferation of hepatoblastoma. Molecular cancer 144 31870368
2001 Drosophila APC2 and Armadillo participate in tethering mitotic spindles to cortical actin. Nature cell biology 141 11584277
2003 CK2 phosphorylation of the armadillo repeat region of beta-catenin potentiates Wnt signaling. The Journal of biological chemistry 138 12700239
2016 Activating mutations in CTNNB1 in aldosterone producing adenomas. Scientific reports 132 26815163
2019 TRAF6 inhibits colorectal cancer metastasis through regulating selective autophagic CTNNB1/β-catenin degradation and is targeted for GSK3B/GSK3β-mediated phosphorylation and degradation. Autophagy 116 30806153
1999 Plakophilin-3, a novel armadillo-like protein present in nuclei and desmosomes of epithelial cells. Journal of cell science 114 10381383
2007 RanBPM, Muskelin, p48EMLP, p44CTLH, and the armadillo-repeat proteins ARMC8alpha and ARMC8beta are components of the CTLH complex. Gene 105 17467196
2015 Pregnancy, Primary Aldosteronism, and Adrenal CTNNB1 Mutations. The New England journal of medicine 98 26397949
1996 Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo. The Journal of biological chemistry 88 8943306
2018 Inhibition of WNT-CTNNB1 signaling upregulates SQSTM1 and sensitizes glioblastoma cells to autophagy blockers. Autophagy 84 29313411
2020 Clinicopathologic and Immunohistochemical Correlates of CTNNB1 Mutated Endometrial Endometrioid Carcinoma. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 78 30702464
2014 R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation. Reproduction (Cambridge, England) 78 25187620
2004 A nuclear function for armadillo/beta-catenin. PLoS biology 77 15024404
2020 CircAGFG1 drives metastasis and stemness in colorectal cancer by modulating YY1/CTNNB1. Cell death & disease 73 32681092
2017 The prevalence of CTNNB1 mutations in primary aldosteronism and consequences for clinical outcomes. Scientific reports 73 28102204
2022 Circ-CTNNB1 drives aerobic glycolysis and osteosarcoma progression via m6A modification through interacting with RBM15. Cell proliferation 72 36181462
1998 Roles of Armadillo, a Drosophila catenin, during central nervous system development. Current biology : CB 68 9635189
2016 Deletion of CTNNB1 in inhibitory circuitry contributes to autism-associated behavioral defects. Human molecular genetics 67 27131348
2021 Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nature genetics 66 34385710
2006 The armadillo protein p0071 regulates Rho signalling during cytokinesis. Nature cell biology 64 17115030
2023 CTNNB1 in neurodevelopmental disorders. Frontiers in psychiatry 56 37009120
2012 CTNNB1 signaling in sertoli cells downregulates spermatogonial stem cell activity via WNT4. PloS one 56 22253774
2017 TTK Inhibitors as a Targeted Therapy for CTNNB1 (β-catenin) Mutant Cancers. Molecular cancer therapeutics 50 28751540
2018 Armadillo repeat containing 12 promotes neuroblastoma progression through interaction with retinoblastoma binding protein 4. Nature communications 47 30026490
2017 Mutant CTNNB1 and histological heterogeneity define metabolic subtypes of hepatoblastoma. EMBO molecular medicine 47 28923827
2015 Slit2 as a β-catenin/Ctnnb1-dependent retrograde signal for presynaptic differentiation. eLife 47 26159615
2013 CTNNB1 in mesenchyme regulates epithelial cell differentiation during Müllerian duct and postnatal uterine development. Molecular endocrinology (Baltimore, Md.) 47 23904126
2004 Identification and in vivo role of the Armadillo-Legless interaction. Development (Cambridge, England) 46 15294866
1999 A screen for identifying genes interacting with armadillo, the Drosophila homolog of beta-catenin. Genetics 46 10581282
2021 MEF2A transcriptionally upregulates the expression of ZEB2 and CTNNB1 in colorectal cancer to promote tumor progression. Oncogene 45 33863999
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2022 Genomic and phenotypic characterization of 404 individuals with neurodevelopmental disorders caused by CTNNB1 variants. Genetics in medicine : official journal of the American College of Medical Genetics 39 36083290
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2015 Microcystic stromal tumour of the ovary: frequent mutations of β-catenin (CTNNB1) in six cases. Histopathology 38 25913412
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2019 Germline Mutations in CTNNB1 Associated With Syndromic FEVR or Norrie Disease. Investigative ophthalmology & visual science 30 30640974
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2013 Beta-catenin versus the other armadillo catenins: assessing our current view of canonical Wnt signaling. Progress in molecular biology and translational science 27 23481204
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2022 m6A demethylase FTO regulate CTNNB1 to promote adipogenesis of chicken preadipocyte. Journal of animal science and biotechnology 22 36461116
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2013 CTNNB1, AXIN1 and APC expression analysis of different medulloblastoma variants. Clinics (Sao Paulo, Brazil) 19 23525311
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