Bridging of β-catenin and glycogen synthase kinase-3β by Axin and inhibition of β-catenin-mediated transcription

Bridging of β-catenin and glycogen synthase kinase-3β by Axin and inhibition of β-catenin-mediated transcription

^*Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0130; ^†Department of Developmental Biology, Stanford University, School of Medicine, Stanford, CA 94305-5427; and Chiron Corporation, Emeryville, CA 94608

Contributed by Lewis T. Williams

Abstract

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

Footnotes

↵ ‡ To whom reprint requests should be addressed. e-mail: chies{at}itsa.ucsf.edu.
ABBREVIATIONS:

GSK-3β,

glycogen synthase kinase 3β;

APC,

adenomatous polyposis coli;

Lef-1,

lymphoid enhancer factor 1;

β-gal,

β-galactosidase