Bridging of beta-catenin and glycogen synthase kinase-3beta by axin and inhibition of beta-catenin-mediated transcription.

Abstract

Axin antagonizes the developmental effects of Wnt in vertebrates. We show here that Axin simultaneously binds two components of the Wnt pathway, beta-catenin and its negative regulator glycogen synthase kinase-3beta. In mammalian cells, Axin inhibits Wnt-1 stimulation of beta-catenin/lymphoid enhancer factor 1-dependent transcription. Axin also blocks beta-catenin-mediated transcription in colon cancer cells that have a mutation in the adenomatous polyposis coli gene. These findings suggest that Axin, by forming a complex with beta-catenin and glycogen synthase kinase-3beta, can block signaling stimulated by Wnt or by adenomatous polyposis coli mutations.