Overview:

Beta-catenins are ubiquitously expressed cytoplasmic proteins. They associate with E-cadherin and thus represent central components of the cadherin cell adhesion complex (1). beta-catenin interacts with TCF and LEF transcription factors and are essential for neural development in the Wingless/Wnt signaling pathway (2). The adenomatous polyposis coli (APC) tumor-suppressor protein, together with Axin and GSK3beta, form a Wnt- regulated signaling complex that mediates phosphorylation dependent degradation of beta-catenin by the proteasome. Specifically, beta-catenin is regulated by sequential phosphorylation of Ser29, Ser33, Ser37 and Thr41 by glycogen synthase kinase 3beta (GSK3beta) (Liu et al. 2002). This hyperphosphorylation promotes the ubiquitylation and targeted degradation of beta-catenin. Mutations in components of this phosphorylation regulated process that prevent beta-catenin hyperphosphorylation by GSK3beta are associated with cancers (4).

References:

1. Morin, P J. et al: Activation of beta-catenen-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science 1997; 275(5307):1787-1790.

2. Ding, Y. et al: Wnt signal transduction: kinase cogs in a nano-machine? Trends Biochem Sci 2002; 27:327-329.

3. Liu, C. et al: Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 2003 108:837-847.

4. Wang, Z H. et al: Phosphorylation of beta-catenin at S33, S37, or T41 can occur in the absence of phosphorylation at T45 in colon cancer cells. 2003 Cancer Res 2003 63:5234-5235.