Down-regulation of beta-catenin by the colorectal tumor suppressor APC requires association with axin and beta-catenin

The tumor suppressor adenomatous polyposis coli (APC) is mutated in familia l adenomatous polyposis and in sporadic colorectal tumors. APC forms a comp lex with beta-catenin, Axin, and glycogen synthase kinase-3 beta and induce s the degradation of beta-catenin. In the present study, me examined whethe r APC association with Axin is required for degradation of beta-catenin. We found that a fragment of APC that induces beta-catenin degradation was ren dered inactive by disruption of its Axin-binding sites. Also, overexpressio n of an Axin fragment spanning the regulator of the G-protein signaling dom ain inhibited APC-mediated beta-catenin degradation. An APC fragment with m utated beta-catenin-binding sites but intact Axin-binding sites also failed to induce degradation of beta-catenin. These results suggest that APC requ ires interaction with Axin and beta-catenin to down-regulate beta-catenin.