title: The RNA-binding protein KSRP promotes decay of beta-catenin mRNA and is inactivated by PI3K-AKT signaling.
abstract: 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.
authors.affiliation: Nazionale per la Ricerca sul Cancro, Genova, Italy. rgherzi@ucsd.edu
authors.forename: Roberto
authors.initials: R
authors.lastname: Gherzi
authors.forename: Michele
authors.initials: M
authors.lastname: Trabucchi
authors.forename: Marco
authors.initials: M
authors.lastname: Ponassi
authors.forename: Tina
authors.initials: T
authors.lastname: Ruggiero
authors.forename: Giorgio
authors.initials: G
authors.lastname: Corte
authors.forename: Christoph
authors.initials: C
authors.lastname: Moroni
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chen
authors.forename: Khalid S
authors.initials: KS
authors.lastname: Khabar
authors.forename: Jens S
authors.initials: JS
authors.lastname: Andersen
authors.forename: Paola
authors.initials: P
authors.lastname: Briata
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics*
chemical_list: D048948:14-3-3 Proteins; D007328:Insulin; C105789:KHSRP protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt