Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance
Authors
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.
Richter, Joel D.
Student Authors
Bryan O'Sullivan-MurphyUMass Chan Affiliations
Research Computing, Information Services DepartmentProgram in Molecular Medicine
Program in Gene Function and Expression
School of Medicine
Document Type
Journal ArticlePublication Date
2012-01-12Keywords
Transcription FactorsmRNA Cleavage and Polyadenylation Factors
PTEN Phosphohydrolase
STAT3 Transcription Factor
Insulin Resistance
Genetics and Genomics
Metadata
Show full item recordAbstract
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.Source
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 siteDOI
10.1371/journal.pgen.1002457Permanent Link to this Item
http://hdl.handle.net/20.500.14038/43972PubMed ID
22253608Related Resources
Link to Article in PubMedRights
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.
ae974a485f413a2113503eed53cd6c53
10.1371/journal.pgen.1002457