Inhibition of Wnt signaling pathway by a novel axin-binding protein

Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3 beta (GSK-3 beta), beta -catenin, DvI, and protein phosp hatase 2A and functions as a scaffold protein in the Wnt signaling pathway. In the Axin complex, GSK-3 beta efficiently phosphorylates beta -catenin, which is then ubiquitinated and degraded by proteasome. We isolated a novel protein that binds to Axin and named it Axam (for Axin associating molecul e). Axam formed a complex with Axin in intact cells and bound directly to A xin. Axam inhibited the complex formation of DvI with Axin and the activity of DvI to suppress GSK-3 beta -dependent phosphorylation of Axin. Furtherm ore, Axam induced the degradation of beta -catenin in SW480 cells and inhib ited Wnt-dependent axis duplication in Xenopus embryos. These results sugge st that Axam regulates the Wnt signaling pathway negatively by inhibiting t he binding of DvI to Axin.