Wnt and its intracellular effector

Axin antagonizes the developmental effects of Wnt in vertebrates. We show here that Axin simultaneously binds two components of the Wnt pathway, ␤-catenin and its negative regulator glycogen synthase kinase-3␤. In mammalian cells, Axin inhibits Wnt-1 stimulation of ␤-catenin͞ lymphoid enhancer factor 1-dependent transcription. Axin also blocks ␤-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 ␤-catenin and glycogen synthase kinase-3␤, can block signaling stimulated by Wnt or by adenomatous polyposis coli mutations.

Genetic studies have identified

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