UMMS Affiliation

Program in Gene Function and Expression; Program in Molecular Medicine; Research Computing, Information Services Department

Date

1-12-2012

Document Type

Article

Medical Subject Headings

Transcription Factors; mRNA Cleavage and Polyadenylation Factors; PTEN Phosphohydrolase; STAT3 Transcription Factor; Insulin Resistance

Disciplines

Genetics and Genomics

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.

Rights and Permissions

Citation: 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

Comments

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.

Related Resources

Link to Article in PubMed

 
 

To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.