Meta-Biol

• Pathways

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).