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Gene Review

CTNNB1  -  catenin (cadherin-associated protein),...

Homo sapiens

Synonyms: Beta-catenin, CTNNB, Catenin beta-1, MRD19, OK/SW-cl.35, ...
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Disease relevance of CTNNB1


Psychiatry related information on CTNNB1

  • Lithium has also been demonstrated to inhibit glycogen synthase kinase 3 beta (GSK-3 beta), an enzyme known to regulate the levels of phosphorylated tau and beta-catenin (both of which may play a role in the neurodegeneration observed in Alzheimer's disease) [7].
  • Wnt signaling in human development: beta-catenin nuclear translocation in fetal lung, kidney, placenta, capillaries, adrenal, and cartilage [8].
  • In addition, exploratory behavior by mice resulted in a similar cleavage of beta-catenin, as well as activation of the Tcf signaling pathway, in hippocampal neurons [9].
  • Thus, while there are no differences between bipolars and controls in prefrontal cortical levels of glycogen synthase kinase-3beta, beta-catenin, or tau, tau isoform levels or phosphorylation states may be modified in bipolar disorder [10].

High impact information on CTNNB1

  • They regulate the activity of enzymes (e.g., glycogen synthase kinase-3, ubiquitin ligase Nedd4-2, phosphomannose mutase-2) and transcription factors (e.g., forkhead transcription factor FKHRL1, beta-catenin, nuclear factor kappaB) [11].
  • Ectopic papillae are innervated in the stabilizing beta-catenin mutant, whereas ectopic Dkk1 causes absence of lingual epithelial innervation [12].
  • A dominant stabilizing mutation of epithelial beta-catenin causes massive overproduction of enlarged fungiform papillae and taste buds [12].
  • The PTEN-Akt pathway probably governs stem cell activation by helping control nuclear localization of the Wnt pathway effector beta-catenin [13].
  • Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin [13].

Chemical compound and disease context of CTNNB1


Biological context of CTNNB1


Anatomical context of CTNNB1

  • Among the 4 cell lines and 87 HCC5 in which we did not detect CTNNB1 mutations, we identified AXIN1 mutations in 3 cell lines and 6 mutations in 5 of the primary HCCs [21].
  • Constitutive activation of the Wnt signaling pathway as a result of genetic alterations of APC, AXIN1, and CTNNB1 has been found in various human cancers, including those of the colon, liver, endometrium, ovary, prostate, and stomach [22].
  • Given that the skin of these adult mice also exhibits signs of de novo hair-follicle morphogenesis, we wondered whether human pilomatricomas might originate from hair matrix cells and whether they might possess beta-catenin-stabilizing mutations [19].
  • Wnt signaling stabilizes beta-catenin, which accumulates in the cytoplasm, binds to 1-cell factor (TCF; also known as lymphocyte enhancer-binding factor, LEF) and then upregulates downstream genes [21].
  • Beta-catenin has been intensively studied in colorectal cancer; however, it is now evident that beta-catenin may be important in cancers of the breast, prostate, and thyroid [23].

Associations of CTNNB1 with chemical compounds

  • Somatic mutation analysis of exon 3 of the beta-catenin gene (CTNNB1) revealed alterations in seven tumours from all five individuals: one at a serine residue (codon 29), three at amino acids adjacent to serine or threonine residues (codons 22, 39, and 44), and three at other amino acids (codons 49, 54, and 56) [24].
  • No mutations were found in the area of the serine/threonine-kinase glycogen synthetase kinase-3-beta-phosphorylation site in exon 3 (CTNNB1) of beta-catenin [25].
  • The NR ligands, vitamin D(3), trans/cis RA, glucocorticoids, and thiazolidines, induce dramatic changes in the physiology of cells harboring high Wnt/beta-catenin/Tcf activity [23].
  • In addition to their essential role in modulating cadherin adhesivity, catenins have more recently been indicated to participate in cell and developmental signaling pathways. beta-Catenin, for example, associates directly with at least two receptor tyrosine kinases and transduces developmental signals within the Wnt pathway [26].
  • At low density, MDCK cells expressing NH2-terminal-deleted beta-catenin mutants are dispersed, more fibroblastic in morphology, and less efficient in forming colonies than parental MDCK cells [27].

Physical interactions of CTNNB1


Enzymatic interactions of CTNNB1

  • STD and TRNOESY NMR studies on the conformation of the oncogenic protein beta-catenin containing the phosphorylated motif DpSGXXpS bound to the beta-TrCP protein [34].
  • Beta catenin may be phosphorylated with implied loss of cadherin binding [35].
  • ILK phosphorylates GSK3 to inhibit its activity and translocates beta-catenin into the nucleus [36].
  • Differences between the interaction of beta-catenin with non-phosphorylated and single-mimicked phosphorylated 20-amino acid residue repeats of the APC protein [37].
  • PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin [38].

Co-localisations of CTNNB1


Regulatory relationships of CTNNB1


Other interactions of CTNNB1


Analytical, diagnostic and therapeutic context of CTNNB1


  1. Beta-catenin mutations in cell lines established from human colorectal cancers. Ilyas, M., Tomlinson, I.P., Rowan, A., Pignatelli, M., Bodmer, W.F. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  2. Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Mirabelli-Primdahl, L., Gryfe, R., Kim, H., Millar, A., Luceri, C., Dale, D., Holowaty, E., Bapat, B., Gallinger, S., Redston, M. Cancer Res. (1999) [Pubmed]
  3. beta-Catenin status predicts a favorable outcome in childhood medulloblastoma: the United Kingdom Children's Cancer Study Group Brain Tumour Committee. Ellison, D.W., Onilude, O.E., Lindsey, J.C., Lusher, M.E., Weston, C.L., Taylor, R.E., Pearson, A.D., Clifford, S.C. J. Clin. Oncol. (2005) [Pubmed]
  4. Novel candidate targets of beta-catenin/T-cell factor signaling identified by gene expression profiling of ovarian endometrioid adenocarcinomas. Schwartz, D.R., Wu, R., Kardia, S.L., Levin, A.M., Huang, C.C., Shedden, K.A., Kuick, R., Misek, D.E., Hanash, S.M., Taylor, J.M., Reed, H., Hendrix, N., Zhai, Y., Fearon, E.R., Cho, K.R. Cancer Res. (2003) [Pubmed]
  5. Genetic and epigenetic alterations of the APC gene in malignant melanoma. Worm, J., Christensen, C., Grønbaek, K., Tulchinsky, E., Guldberg, P. Oncogene (2004) [Pubmed]
  6. Activation of beta-catenin by hypoxia in hepatocellular carcinoma contributes to enhanced metastatic potential and poor prognosis. Liu, L., Zhu, X.D., Wang, W.Q., Shen, Y., Qin, Y., Ren, Z.G., Sun, H.C., Tang, Z.Y. Clin. Cancer Res. (2010) [Pubmed]
  7. Lithium at 50: have the neuroprotective effects of this unique cation been overlooked? Manji, H.K., Moore, G.J., Chen, G. Biol. Psychiatry (1999) [Pubmed]
  8. Wnt signaling in human development: beta-catenin nuclear translocation in fetal lung, kidney, placenta, capillaries, adrenal, and cartilage. Eberhart, C.G., Argani, P. Pediatr. Dev. Pathol. (2001) [Pubmed]
  9. NMDA-Receptor Activation Induces Calpain-Mediated beta-Catenin Cleavages for Triggering Gene Expression. Abe, K., Takeichi, M. Neuron (2007) [Pubmed]
  10. Glycogen synthase kinase-3beta, beta-catenin, and tau in postmortem bipolar brain. Lesort, M., Greendorfer, A., Stockmeier, C., Johnson, G.V., Jope, R.S. Journal of neural transmission (Vienna, Austria : 1996) (1999) [Pubmed]
  11. (Patho)physiological Significance of the Serum- and Glucocorticoid-Inducible Kinase Isoforms. Lang, F., B??hmer, C., Palmada, M., Seebohm, G., Strutz-Seebohm, N., Vallon, V. Physiol. Rev. (2006) [Pubmed]
  12. Wnt-beta-catenin signaling initiates taste papilla development. Liu, F., Thirumangalathu, S., Gallant, N.M., Yang, S.H., Stoick-Cooper, C.L., Reddy, S.T., Andl, T., Taketo, M.M., Dlugosz, A.A., Moon, R.T., Barlow, L.A., Millar, S.E. Nat. Genet. (2007) [Pubmed]
  13. PTEN-deficient intestinal stem cells initiate intestinal polyposis. He, X.C., Yin, T., Grindley, J.C., Tian, Q., Sato, T., Tao, W.A., Dirisina, R., Porter-Westpfahl, K.S., Hembree, M., Johnson, T., Wiedemann, L.M., Barrett, T.A., Hood, L., Wu, H., Li, L. Nat. Genet. (2007) [Pubmed]
  14. Geldanamycin abrogates ErbB2 association with proteasome-resistant beta-catenin in melanoma cells, increases beta-catenin-E-cadherin association, and decreases beta-catenin-sensitive transcription. Bonvini, P., An, W.G., Rosolen, A., Nguyen, P., Trepel, J., Garcia de Herreros, A., Dunach, M., Neckers, L.M. Cancer Res. (2001) [Pubmed]
  15. The ubiquitin-proteasome pathway and serine kinase activity modulate adenomatous polyposis coli protein-mediated regulation of beta-catenin-lymphocyte enhancer-binding factor signaling. Easwaran, V., Song, V., Polakis, P., Byers, S. J. Biol. Chem. (1999) [Pubmed]
  16. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Jaiswal, A.S., Marlow, B.P., Gupta, N., Narayan, S. Oncogene (2002) [Pubmed]
  17. Molecular analysis of sulindac-resistant adenomas in familial adenomatous polyposis. Keller, J.J., Offerhaus, G.J., Drillenburg, P., Caspers, E., Musler, A., Ristimäki, A., Giardiello, F.M. Clin. Cancer Res. (2001) [Pubmed]
  18. Nuclear translocation of beta-catenin in hereditary and carcinogen-induced intestinal adenomas. Sheng, H., Shao, J., Williams, C.S., Pereira, M.A., Taketo, M.M., Oshima, M., Reynolds, A.B., Washington, M.K., DuBois, R.N., Beauchamp, R.D. Carcinogenesis (1998) [Pubmed]
  19. A common human skin tumour is caused by activating mutations in beta-catenin. Chan, E.F., Gat, U., McNiff, J.M., Fuchs, E. Nat. Genet. (1999) [Pubmed]
  20. Diverse mechanisms of beta-catenin deregulation in ovarian endometrioid adenocarcinomas. Wu, R., Zhai, Y., Fearon, E.R., Cho, K.R. Cancer Res. (2001) [Pubmed]
  21. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Satoh, S., Daigo, Y., Furukawa, Y., Kato, T., Miwa, N., Nishiwaki, T., Kawasoe, T., Ishiguro, H., Fujita, M., Tokino, T., Sasaki, Y., Imaoka, S., Murata, M., Shimano, T., Yamaoka, Y., Nakamura, Y. Nat. Genet. (2000) [Pubmed]
  22. Constitutive activation of the Wnt signaling pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma. Sunaga, N., Kohno, T., Kolligs, F.T., Fearon, E.R., Saito, R., Yokota, J. Genes Chromosomes Cancer (2001) [Pubmed]
  23. Interaction of nuclear receptors with the Wnt/beta-catenin/Tcf signaling axis: Wnt you like to know? Mulholland, D.J., Dedhar, S., Coetzee, G.A., Nelson, C.C. Endocr. Rev. (2005) [Pubmed]
  24. Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. Xu, B., Yoshimoto, K., Miyauchi, A., Kuma, S., Mizusawa, N., Hirokawa, M., Sano, T. J. Pathol. (2003) [Pubmed]
  25. Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer. Günther, K., Brabletz, T., Kraus, C., Dworak, O., Reymond, M.A., Jung, A., Hohenberger, W., Kirchner, T., Köckerling, F., Ballhausen, W.G. Dis. Colon Rectum (1998) [Pubmed]
  26. beta-Catenin associates with the actin-bundling protein fascin in a noncadherin complex. Tao, Y.S., Edwards, R.A., Tubb, B., Wang, S., Bryan, J., McCrea, P.D. J. Cell Biol. (1996) [Pubmed]
  27. NH2-terminal deletion of beta-catenin results in stable colocalization of mutant beta-catenin with adenomatous polyposis coli protein and altered MDCK cell adhesion. Barth, A.I., Pollack, A.L., Altschuler, Y., Mostov, K.E., Nelson, W.J. J. Cell Biol. (1997) [Pubmed]
  28. Analysis of the signaling activities of localization mutants of beta-catenin during axis specification in Xenopus. Miller, J.R., Moon, R.T. J. Cell Biol. (1997) [Pubmed]
  29. Insulin-like growth factor 1 regulates the location, stability, and transcriptional activity of beta-catenin. Playford, M.P., Bicknell, D., Bodmer, W.F., Macaulay, V.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  30. Axin-dependent phosphorylation of the adenomatous polyposis coli protein mediated by casein kinase 1epsilon. Rubinfeld, B., Tice, D.A., Polakis, P. J. Biol. Chem. (2001) [Pubmed]
  31. The presenilin 1 protein is a component of a high molecular weight intracellular complex that contains beta-catenin. Yu, G., Chen, F., Levesque, G., Nishimura, M., Zhang, D.M., Levesque, L., Rogaeva, E., Xu, D., Liang, Y., Duthie, M., St George-Hyslop, P.H., Fraser, P.E. J. Biol. Chem. (1998) [Pubmed]
  32. The transmembrane receptor protein tyrosine phosphatase DEP1 interacts with p120(ctn). Holsinger, L.J., Ward, K., Duffield, B., Zachwieja, J., Jallal, B. Oncogene (2002) [Pubmed]
  33. beta-Catenin is a Nek2 substrate involved in centrosome separation. Bahmanyar, S., Kaplan, D.D., Deluca, J.G., Giddings, T.H., O'Toole, E.T., Winey, M., Salmon, E.D., Casey, P.J., Nelson, W.J., Barth, A.I. Genes Dev. (2008) [Pubmed]
  34. STD and TRNOESY NMR studies on the conformation of the oncogenic protein beta-catenin containing the phosphorylated motif DpSGXXpS bound to the beta-TrCP protein. Megy, S., Bertho, G., Gharbi-Benarous, J., Evrard-Todeschi, N., Coadou, G., Ségéral, E., Iehle, C., Quéméneur, E., Benarous, R., Girault, J.P. J. Biol. Chem. (2005) [Pubmed]
  35. Sequential changes in cadherin-catenin expression associated with the progression and heterogeneity of primary oesophageal squamous carcinoma. Sanders, D.S., Bruton, R., Darnton, S.J., Casson, A.G., Hanson, I., Williams, H.K., Jankowski, J. Int. J. Cancer (1998) [Pubmed]
  36. Signaling through beta-catenin and Lef/Tcf. Novak, A., Dedhar, S. Cell. Mol. Life Sci. (1999) [Pubmed]
  37. Differences between the interaction of beta-catenin with non-phosphorylated and single-mimicked phosphorylated 20-amino acid residue repeats of the APC protein. Tickenbrock, L., Kössmeier, K., Rehmann, H., Herrmann, C., Müller, O. J. Mol. Biol. (2003) [Pubmed]
  38. PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin. Ilan, N., Mahooti, S., Rimm, D.L., Madri, J.A. J. Cell. Sci. (1999) [Pubmed]
  39. LZTS2 Is a Novel {beta}-Catenin-Interacting Protein and Regulates the Nuclear Export of {beta}-Catenin. Thyssen, G., Li, T.H., Lehmann, L., Zhuo, M., Sharma, M., Sun, Z. Mol. Cell. Biol. (2006) [Pubmed]
  40. Nuclear accumulation of full-length and truncated adenomatous polyposis coli protein in tumor cells depends on proliferation. Fagman, H., Larsson, F., Arvidsson, Y., Meuller, J., Nordling, M., Martinsson, T., Helmbrecht, K., Brabant, G., Nilsson, M. Oncogene (2003) [Pubmed]
  41. ERBIN associates with p0071, an armadillo protein, at cell-cell junctions of epithelial cells. Izawa, I., Nishizawa, M., Tomono, Y., Ohtakara, K., Takahashi, T., Inagaki, M. Genes Cells (2002) [Pubmed]
  42. Molecular organization of tight and adherens junctions in the human placental vascular tree. Leach, L., Lammiman, M.J., Babawale, M.O., Hobson, S.A., Bromilou, B., Lovat, S., Simmonds, M.J. Placenta (2000) [Pubmed]
  43. M-cadherin and beta-catenin participate in differentiation of rat satellite cells. Wróbel, E., Brzóska, E., Moraczewski, J. Eur. J. Cell Biol. (2007) [Pubmed]
  44. Promoter swapping between the genes for a novel zinc finger protein and beta-catenin in pleiomorphic adenomas with t(3;8)(p21;q12) translocations. Kas, K., Voz, M.L., Röijer, E., Aström, A.K., Meyen, E., Stenman, G., Van de Ven, W.J. Nat. Genet. (1997) [Pubmed]
  45. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Tetsu, O., McCormick, F. Nature (1999) [Pubmed]
  46. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Morin, P.J., Sparks, A.B., Korinek, V., Barker, N., Clevers, H., Vogelstein, B., Kinzler, K.W. Science (1997) [Pubmed]
  47. Tumor suppressor PTEN inhibits nuclear accumulation of beta-catenin and T cell/lymphoid enhancer factor 1-mediated transcriptional activation. Persad, S., Troussard, A.A., McPhee, T.R., Mulholland, D.J., Dedhar, S. J. Cell Biol. (2001) [Pubmed]
  48. Beta-catenin mutations in biliary tract cancers: a population-based study in China. Rashid, A., Gao, Y.T., Bhakta, S., Shen, M.C., Wang, B.S., Deng, J., Fraumeni, J.F., Hsing, A.W. Cancer Res. (2001) [Pubmed]
  49. Wnt/beta-catenin and 3',5'-cyclic adenosine 5'-monophosphate/protein kinase A signaling pathways alterations and somatic beta-catenin gene mutations in the progression of adrenocortical tumors. Gaujoux, S., Tissier, F., Groussin, L., Libé, R., Ragazzon, B., Launay, P., Audebourg, A., Dousset, B., Bertagna, X., Bertherat, J. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  50. HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. Li, Y., Zhang, X., Polakiewicz, R.D., Yao, T.P., Comb, M.J. J. Biol. Chem. (2008) [Pubmed]
  51. Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts. Georgakopoulos, A., Marambaud, P., Efthimiopoulos, S., Shioi, J., Cui, W., Li, H.C., Schütte, M., Gordon, R., Holstein, G.R., Martinelli, G., Mehta, P., Friedrich, V.L., Robakis, N.K. Mol. Cell (1999) [Pubmed]
  52. Somatic mutations of WNT/wingless signaling pathway components in primitive neuroectodermal tumors. Koch, A., Waha, A., Tonn, J.C., Sörensen, N., Berthold, F., Wolter, M., Reifenberger, J., Hartmann, W., Friedl, W., Reifenberger, G., Wiestler, O.D., Pietsch, T. Int. J. Cancer (2001) [Pubmed]
  53. Target genes of the WNT/beta-catenin pathway in Wilms tumors. Zirn, B., Samans, B., Wittmann, S., Pietsch, T., Leuschner, I., Graf, N., Gessler, M. Genes Chromosomes Cancer (2006) [Pubmed]
  54. Mutation analysis of CTNNB1 (beta-catenin) and AXIN1, the components of Wnt pathway, in cervical carcinomas. Su, T.H., Chang, J.G., Yeh, K.T., Lin, T.H., Lee, T.P., Chen, J.C., Lin, C.C. Oncol. Rep. (2003) [Pubmed]
  55. Assignment of the human beta-catenin gene (CTNNB1) to 3p22-->p21.3 by fluorescence in situ hybridization. van Hengel, J., Nollet, F., Berx, G., van Roy, N., Speleman, F., van Roy, F. Cytogenet. Cell Genet. (1995) [Pubmed]
  56. Mutations in exon 3 of the beta-catenin gene are rare in melanoma cell lines. Pollock, P.M., Hayward, N. Melanoma Res. (2002) [Pubmed]
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