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

• DOI: 10.1371/journal.pbio.0050005
• Publication Date: 2006-12-15T05:22:36Z
• Authors: Roberto Gherzi; Michele Trabucchi; Marco Ponassi; Tina Ruggiero; Giorgio Corte; Christoph Moroni; Ching-Yi Chen; Khalid S Khabar; Jens S Andersen; Paola Briata
• Keywords: QH301-705.5; RNA Stability; Messenger; Cell Line; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 1-Phosphatidylinositol 3-Kinase; Animals; Humans; Insulin; RNA, Messenger; Biology (General); Phosphorylation; beta Catenin; 0303 health sciences; RNA-Binding Proteins; 3. Good health; Enzyme Activation; Wnt Proteins; 14-3-3 Proteins; Gene Expression Regulation; Trans-Activators; RNA; Proto-Oncogene Proteins c-akt; Research Article; Protein Binding; Signal Transduction

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.