title: Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance.
abstract: The cytoplasmic polyadenylation element binding protein CPEB1 (CPEB) regulates germ cell development, synaptic plasticity, and cellular senescence. A microarray analysis of mRNAs regulated by CPEB unexpectedly showed that several encoded proteins are involved in insulin signaling. An investigation of Cpeb1 knockout mice revealed that the expression of two particular negative regulators of insulin action, PTEN and Stat3, were aberrantly increased. Insulin signaling to Akt was attenuated in livers of CPEB-deficient mice, suggesting that they might be defective in regulating glucose homeostasis. Indeed, when the Cpeb1 knockout mice were fed a high-fat diet, their livers became insulin-resistant. Analysis of HepG2 cells, a human liver cell line, depleted of CPEB demonstrated that this protein directly regulates the translation of PTEN and Stat3 mRNAs. Our results show that CPEB regulated translation is a key process involved in insulin signaling.
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Ilya M
authors.initials: IM
authors.lastname: Alexandrov
authors.forename: Maria
authors.initials: M
authors.lastname: Ivshina
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Jung
authors.forename: Randall
authors.initials: R
authors.lastname: Friedline
authors.forename: Hwi Jin
authors.initials: HJ
authors.lastname: Ko
authors.forename: Mei
authors.initials: M
authors.lastname: Xu
authors.forename: Bryan
authors.initials: B
authors.lastname: O'Sullivan-Murphy
authors.forename: Rita
authors.initials: R
authors.lastname: Bortell
authors.forename: Yen-Tsung
authors.initials: YT
authors.lastname: Huang
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Urano
authors.forename: Jason K
authors.initials: JK
authors.lastname: Kim
authors.forename: Joel D
authors.initials: JD
authors.lastname: Richter
mesh_terms: D000818:Animals; D002460:Cell Line; D059305:Diet, High-Fat; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D011132:Polyribosomes / Q000235:genetics; D014176:Protein Biosynthesis / Q000235:genetics*; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
chemical_list: C490386:CPEB1 protein, human; C490387:Cpeb1 protein, mouse; D007328:Insulin; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; D051059:PTEN Phosphohydrolase; D005947:Glucose