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).
Laurent-Puig, P, Legoix, P, Bluteau, O, Belghiti, J, Franco, D, Binot, F, Monges, G, Thomas, G, Bioulac-Sage, P, Zucman-Rossi, J
Amit, S, Hatzubai, A, Birman, Y, Andersen, JS, Ben-Shushan, E, Mann, M, Ben-Neriah, Y, Alkalay, I
Morin, PJ, Sparks, AB, Korinek, V, Barker, N, Clevers, HC, Vogelstein, B, Kinzler, KW
Nhieu, JT, Renard, CA, Wei, Y, Cherqui, D, Zafrani, ES, Buendia, MA
Polakis, P
Koesters, R, Niggli, F, von Knebel Doeberitz, M, Stallmach, T
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