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.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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14-3-3 Proteins / genetics
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14-3-3 Proteins / metabolism
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Animals
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Cell Line
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Enzyme Activation / drug effects
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Gene Expression Regulation
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Humans
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Insulin / pharmacology
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Mice
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Phosphatidylinositol 3-Kinases / genetics
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Phosphatidylinositol 3-Kinases / metabolism*
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Phosphorylation
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Protein Binding
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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RNA Stability*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism*
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Signal Transduction*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Wnt Proteins / metabolism
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beta Catenin / genetics*
Substances
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14-3-3 Proteins
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Insulin
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KHSRP protein, human
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RNA, Messenger
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RNA-Binding Proteins
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Trans-Activators
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Wnt Proteins
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beta Catenin
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt