The RNA-Binding Protein KSRP Promotes Decay of - -Catenin mRNA and Is Inactivated by PI3K-AKT Si

-catenin plays an essential role in several biological events including cell fate determination, cell proliferation, and transformation. Here we report that -catenin is encoded by a labile transcript whose half-life is prolonged by Wnt and phosphatidylinositol 3-kinaseAKT signaling. AKT phosphorylates the mRNA decay-promoting factor KSRP at a unique serine residue, induces its association with the multifunctional protein 14-3-3, and prevents KSRP interaction with the exoribonucleolytic complex exosome. This impairs KSRP''s ability to promote rapid mRNA decay. Our results uncover an unanticipated level of control of -catenin expression pointing to KSRP as a required factor to ensure rapid degradation of -catenin in unstimulated cells. We propose KSRP phosphorylation as a link between phosphatidylinositol 3-kinaseAKT signaling and -catenin accumulation.