CTNNB1 S45 mutants aren't phosphorylated by CK1alpha

Stable Identifier
Reaction [transition]
Homo sapiens
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Missense or deletion mutations at Ser45 abolish the CK1alpha phosphorylation site of beta-catenin, which, via its critical role in providing a priming site for GSK3 phosphorylation of three other residues, prevents its ubiquitin-mediated degradation (Morin et al, 1997; Amit et al, 2002). S45 mutant forms of beta-catenin show enhanced nuclear localization, supershift TCF-DNA complexes in vitro and support enhanced transcriptional activity as assessed by reporter assay (Morin et al, 1997; Koesters et al, 2003; Laurent-Puig et al, 2003). Nuclear accumulation of mutant beta-catenin is also associated with increased cell proliferation (Nhieu et al, 1999). S45 gain-of-function mutants of beta-catenin have been identified in colorectal and hepatocellular carcinomas, soft tissue cancer and Wilms Tumors, among others (reviewed in Polakis, 2000).
Literature References
PubMed ID Title Journal Year
12000790 Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway

Andersen, JS, Birman, Y, Mann, M, Ben-Shushan, E, Alkalay, I, Hatzubai, A, Amit, S, Ben-Neriah, Y

Genes Dev 2002
11375957 Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

Bluteau, O, Monges, G, Bioulac-Sage, P, Binot, F, Franco, D, Thomas, G, Belghiti, J, Laurent-Puig, P, Zucman-Rossi, J, Legoix, P

Gastroenterology 2001
9065402 Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC

Barker, N, Clevers, HC, Morin, PJ, Kinzler, KW, Vogelstein, B, Korinek, V, Sparks, AB

Science 1997
10487827 Nuclear accumulation of mutated beta-catenin in hepatocellular carcinoma is associated with increased cell proliferation

Zafrani, ES, Renard, CA, Wei, Y, Cherqui, D, Nhieu, JT, Buendia, MA

Am. J. Pathol. 1999
10921899 Wnt signaling and cancer

Polakis, P

Genes Dev. 2000
12474228 Nuclear accumulation of beta-catenin protein in Wilms' tumours

Koesters, R, Niggli, F, von Knebel Doeberitz, M, Stallmach, T

J. Pathol. 2003
Normal reaction
Functional status

Loss of function of CTNNB1 S45 mutants:AXIN:GSK3:CK1alpha:APC:PP2A:AMER1 complex [cytosol]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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