Beta-catenin

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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
Symbol(s)	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.

[edit] 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.

[edit] 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]

[edit] 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).

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 kinases^[3] 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]

[edit] 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.

[edit] See also

• Catenin

[edit] 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

[edit] References

[edit] Further reading