Program in Gene Function and Expression; Program in Molecular Medicine; Research Computing, Information Services Department
Transcription Factors; mRNA Cleavage and Polyadenylation Factors; PTEN Phosphohydrolase; STAT3 Transcription Factor; Insulin Resistance
Genetics and Genomics
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.
Rights and Permissions
Copyright: © 2012 Alexandrov et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DOI of Published Version
Alexandrov IM, Ivshina M, Jung DY, Friedline R, Ko HJ, et al. (2012) Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance. PLoS Genet 8(1): e1002457. doi:10.1371/journal.pgen.1002457 Link to article on publisher's site
Alexandrov, Ilya M.; Ivshina, Maria; Jung, Dae Young; Friedline, Randall H.; Ko, Hwi Jin; Xu, Mei; O'Sullivan-Murphy, Bryan; Bortell, Rita; Huang, Yen-Tsung; Urano, Fumihiko; Kim, Jason K.; and Richter, Joel D., "Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance" (2012). Program in Gene Function and Expression Publications and Presentations. 183.