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

Abstract

Axin forms a complex with adenomatous polyposis coli gene product, glycogen synthase kinase-3β (GSK-3β), β-catenin, Dvl, and protein phosphatase 2A and functions as a scaffold protein in the Wnt signaling pathway. In the Axin complex, GSK-3β efficiently phosphorylates β-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 molecule). Axam formed a complex with Axin in intact cells and bound directly to Axin. Axam inhibited the complex formation of Dvl with Axin and the activity of Dvl to suppress GSK-3β-dependent phosphorylation of Axin. Furthermore, Axam induced the degradation of β-catenin in SW480 cells and inhibited Wnt-dependent axis duplication in Xenopus embryos. These results suggest that Axam regulates the Wnt signaling pathway negatively by inhibiting the binding of Dv1 to Axin.