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Gherzi, Roberto; Trabucchi, Michele; Ponassi, Marco; Ruggiero, Tina; Corte, Giorgio; Moroni, Christoph; Chen, Ching-Yi; Khabar, Khalid S; Andersen, Jens S; Briata, Paola
PLoS biology, 12/2006, Letnik: 5, Številka: 1Journal Article
Beta-catenin plays an essential role in several biological events including cell fate determination, cell proliferation, and transformation. Here we report that beta-catenin is encoded by a labile transcript whose half-life is prolonged by Wnt and phosphatidylinositol 3-kinase-AKT 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 beta-catenin expression pointing to KSRP as a required factor to ensure rapid degradation of beta-catenin in unstimulated cells. We propose KSRP phosphorylation as a link between phosphatidylinositol 3-kinase-AKT signaling and beta-catenin accumulation.
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