BRIDGING OF BETA-CATENIN AND GLYCOGEN-SYNTHASE KINASE-3-BETA BY AXIN AND INHIBITION OF BETA-CATENIN-MEDIATED TRANSCRIPTION

Axin antagonizes the developmental effects of Wnt in vertebrates, We s how here that Axin simultaneously binds two components of the Wnt path way, beta-catenin and its negative regulator glycogen synthase kinase- 3 beta, In mammalian cells, Axin inhibits Wnt-1 stimulation of beta-ca tenin/lymphoid enhancer factor 1-dependent transcription, Axin also bl ocks beta-catenin-mediated transcription in colon cancer cells that ha ve a mutation in the adenomatous polyposis coli gene, These findings s uggest that Axin, by forming a complex with beta-catenin and glycogen synthase kinase-3 beta, can block signaling stimulated by Wnt or by ad enomatous polyposis coli mutations.