COMMUNICATION - AXIN, A NEGATIVE REGULATOR OF THE WNT SIGNALING PATHWAY, DIRECTLY INTERACTS WITH ADENOMATOUS POLYPOSIS-COLI AND REGULATES THE STABILIZATION OF BETA-CATENIN

The regulators of G protein signaling (RGS) domain of Axin, a negative regulator of the Wnt signaling pathway, made a complex with full-leng th adenomatous polyposis coli (APC) in COS, 293, and L cells but not w ith truncated APC in SW480 or DLD-1 cells. The RGS domain directly int eracted with the region containing the 20-amino acid repeats but not w ith that containing the 15-amino acid repeats of APC, although both re gions are known to bind to beta-catenin. In the region containing seve n 20-amino acid repeats, the region containing the latter five repeats bound to the RGS domain of Axin. Axin and beta-catenin simultaneously interacted with APC. Furthermore, Axin stimulated the degradation of beta-catenin in COS cells. Taken together with our recent observations that Axin directly interacts with glycogen synthase kinase-3 beta (GS K-3 beta) and beta-catenin and that it promotes GSK-3 beta-dependent p hosphorylation of beta-catenin, these results suggest that Axin, APC, GSK-3 beta, and beta-catenin make a tetrameric complex, resulting in t he regulation of the stabilization of beta-catenin.