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07-SEPTEMBER-2008 03:17:44 - catenin Catenin cadherin-associated protein, beta 1, 88kDa PDB rendering based on 1dow. Available structures: 1dow, 1g3j, 1i7w, 1i7x, 1jdh, 1jpp, 1jpw, 1luj, 1m1e, 1qz7, 1t08, 1th1, 1v18, 2bct, 2gl7, 3bct Identifiers Symbols CTNNB1; CTNNB; FLJ25606 External IDs OMIM: 116806 MGI: 88276 HomoloGene: 1434 Gene ontology Molecular function: chromatin binding transcription factor activity transcription coactivator activity signal transducer activity structural molecule activity binding alpha-catenin binding cadherin binding androgen receptor binding Cellular component: membrane fraction nucleus transcription factor complex cytoplasm cytoskeleton plasma membrane cell-cell adherens junction basolateral plasma membrane lateral plasma membrane lamellipodium microvillus membrane apical part of cell Biological process: negative regulation of transcription from RNA polymerase II promoter cellular morphogenesis during differentiation skeletal development patterning of blood vessels endoderm formation cell fate specification cell fate determination endodermal cell fate commitment synaptic transmission ectoderm development heart development dorsal/ventral axis specification proximal/distal pattern formation gastrulation sensu Mammalia Wnt receptor signaling pathway morphogenesis of embryonic epithelium cell-cell adhesion hemopoiesis osteoclast differentiation lung development androgen receptor signaling pathway positive regulation of epithelial cell differentiation forebrain development pancreas development embryonic hindlimb morphogenesis embryonic arm morphogenesis regulation of cell proliferation odontogenesis sensu Vertebrata embryonic digit morphogenesis bone resorption negative regulation of cell differentiation positive regulation of osteoblast differentiation negative regulation of osteoclast differentiation positive regulation of transcription from RNA polymerase II promoter cell maturation synaptic vesicle transport synapse organization and biogenesis RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 1499 12387 Ensembl ENSG00000168036 ENSMUSG00000006932 Uniprot P35222 Q3UZT7 Refseq XM_001133660 mRNA XP_001133660 protein NM_007614 mRNA NP_031640 protein Location Chr 3: 41.22 - 41.26 Mb Chr 9: 120.78 - 120.81 Mb Pubmed search 1 2 Beta-catenin is a subunit of the cadherin protein complex. In Drosophila, the homologous protein is called armadillo. Beta-catenin has been implicated as an integral component in the Wnt signaling pathway. Contents 1 Function 2 Role in liver biology 3 Interactions of beta-catenin with other proteins 4 Role of beta-catenin in the Wnt signaling pathway 5 See also 6 External links 7 References 8 Further reading Function When beta-catenin was sequenced it was found to be a member of the armadillo family of proteins. These proteins have multiple copies of the so-called armadillo repeat domain which is specialized for protein-protein binding. An increase in beta-catenin production has been noted in those people who have Basal Cell Carcinoma and leads to the increase in proliferation of related tumors.1 When beta-catenin is not associated with cadherins and alpha-catenin, it can interact with other proteins such as ICAT and APC. Role in liver biology Recent evidence suggests that beta-catenin plays an important role in various aspects of liver biology including liver development both embryonic and postnatal, liver regeneration following partial hepatectomy. HGF-induced hepatpomegaly, liver zonation, and pathogenesis of liver cancer.2 Interactions of beta-catenin with other proteins Figure 2. Beta-catenin β can interact with several different proteins inside cells. The interaction of beta-catenin with other proteins is often regulated by the reversible attachment of phosphate P. Figure 2. Beta-catenin β can interact with several different proteins inside cells. The interaction of beta-catenin with other proteins is often regulated by the reversible attachment of phosphate P. As mentioned above, beta-catenin contains armadillo repeats and is able to bind to other proteins. Inside cells, beta-catenin can be found in complexes with cadherins, transcription factors TF in Figure 2 and other proteins such as axin, a component of the Wnt signalling pathway. The ability of beta-catenin to bind to other proteins is regulated by tyrosine kinases3 and serine kinases such as GSK-3.4 When beta-catenin is not assembled in complexes with cadherins, it can form a complex with axin. While bound to axin, beta-catenin can be phosphorylated by GSK-3, which creates a signal for the rapid ubiquitin-dependent degradation of beta-catenin by proteosomes. Various signals such as the Wnt signalling pathway can inhibit GSK-3-mediated phosphorylation of beta-catenin,5 allowing beta-catenin to go to the cell nucleus, interact with transcription factors, and regulate gene transcription. Beta-catenin can be phosphorylated by other kinases such as protein kinase A PKA. Phosphorylation of beta-catenin by PKA has been associated with reduced degradation of beta-catenin, increased levels of beta-catenin in the nucleus and interaction of beta-catenin with TCF family transcription factors to regulate gene expression.6 Role of beta-catenin in the Wnt signaling pathway When Wnt is not present, GSK3 a kinase constitutively phosphorylates the beta-catenin protein. Beta-catenin is associated with Axin scaffolding protein complexed with GSK3 and APC adenomatosis polyposis coli. The creation of said complex acts to substantially increase the phosphorylation of beta-catenin by facilitating the action of GSK3. When beta-catenin is phosphorylated it is degraded and thus will not build up in the cell to a significant level. When Wnt binds to Frizzled Fz, its receptor, dishevelled Dsh is recruited to the membrane. GSK3 is inhibited by the activation of Dsh by Fz. Because of this, beta-catenin is permited to build up in the cytosol and can be subsequently translocated into the nucleus to perform a variety of functions. It can act in conjunction with TCF to activate specific genes as well as cause the export of TCF from the nucleus. See also Catenin External links MeSH Beta+Catenin A diverse set of proteins modulate the canonical Wnt/beta-catenin signaling pathway. at cancer.gov The role of beta-catenin in signal transduction, cell fate determination and trans-differentiation at nih.gov References ^ G. Saldanha, V. Ghura, L. Potter and A. Fletcher. Nuclear beta-catenin in basal cell carcinoma correlates with increased proliferation in The British Journal of Dermatology 2004 Volume 151, pages 157-164. Entrez PubMed 15270885 ^ Thompson MD, Monga SP 2007. WNT/beta-catenin signaling in liver health and disease. Hepatology 45 5: 1298-305. doi:10.1002/hep.21651. PMID 17464972. ^ J. Lilien and J. Balsamo The regulation of cadherin-mediated adhesion by tyrosine phosphorylation/dephosphorylation of beta-catenin in Current opinion in cell biology 2005 Volume 17, pages 459-465. Entrez PubMed 16099633 ^ M. D. Castellone, H. Teramoto, B. O. Williams, K. M. Druey, J. S. Gutkind. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis in Science 2005 Volume 310, pages 1504-1510. Entrez PubMed 16293724 ^ X. Liu, J. S. Rubin and A. R. Kimmel. Rapid, Wnt-induced changes in GSK3beta associations that regulate beta-catenin stabilization are mediated by Galpha proteins in Current Biology 2005 Volume 15, pages 1989-1997. Entrez PubMed 16303557 ^ S. Hino, C. Tanji, K. I. Nakayama and A. Kikuchi Phosphorylation of beta-catenin by cyclic AMP-dependent protein kinase stabilizes beta-catenin through inhibition of its ubiquitination in Molecular and Cellular Biology 2005 Volume 20, pages 9063-9072. Entrez PubMed 16199882 Further reading Kikuchi A 2000. Regulation of beta-catenin signaling in the Wnt pathway.. Biochem. Biophys. Res. Commun. 268 2: 243-8. doi:10.1006/bbrc.1999.1860. PMID 10679188. Wilson PD 2001. Polycystin: new aspects of structure, function, and regulation.. J. Am. Soc. Nephrol. 12 4: 834-45. PMID 11274246. Kalluri R, Neilson EG 2004. Epithelial-mesenchymal transition and its implications for fibrosis.. J. Clin. Invest. 112 12: 1776-84. doi:10.1172/JCI200320530. PMID 14679171. De Ferrari GV, Moon RT 2007. The ups and downs of Wnt signaling in prevalent neurological disorders.. Oncogene 25 57: 7545-53. doi:10.1038/sj.onc.1210064. PMID 17143299. v d e Proteins of the cytoskeleton Microfilaments Actins - Actin-binding proteins - Actinin - Arp2/3 complex - Cofilin - Destrin - Gelsolin - Myosins - Profilin - Tropomodulin - Troponin T, C, I - Tropomyosin - Wiskott-Aldrich syndrome protein Intermediate filaments type 1 and 2 Cytokeratin, type I, type II - type 3 Desmin, GFAP, Peripherin, Vimentin - type 4 Internexin, Nestin, Neurofilament, Synemin, Syncoilin - type 5 Lamin A, B Microtubules Dyneins - Kinesins - MAPs Tau protein, Dynamin - Tubulins - Stathmin - Tektin Catenins Alpha catenin - Beta catenin - Plakoglobin gamma catenin - Delta catenin Nonhuman Major sperm proteins - Prokaryotic cytoskeleton Crescentin, FtsZ, MreB Other APC - Dystrophin Dystroglycan - plakin Desmoplakin, Plectin - Spectrin - Talin - Utrophin - Vinculin Retrieved from http://en..org/wiki/Beta-catenin Categories: Genes on chromosome 3 | Human proteins | Signal transduction | Proteins Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page This page was last modified on 8 July 2008, at 02:38
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