Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance

Ilya M. Alexandrov, Maria Ivshina, Dae Young Jung, Randall Friedline, Hwi Jin Ko, Mei Xu, Bryan O'Sullivan-Murphy, Rita Bortell, Yen Tsung Huang, Fumihiko Urano, Jason K. Kim, Joel D. Richter

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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.

Original languageEnglish
Article numbere1002457
JournalPLoS genetics
Volume8
Issue number1
DOIs
StatePublished - Jan 2012
Externally publishedYes

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    Alexandrov, I. M., Ivshina, M., Jung, D. Y., Friedline, R., Ko, H. J., Xu, M., O'Sullivan-Murphy, B., Bortell, R., Huang, Y. T., Urano, F., Kim, J. K., & Richter, J. D. (2012). Cytoplasmic polyadenylation element binding protein deficiency stimulates PTEN and Stat3 mRNA translation and induces hepatic insulin resistance. PLoS genetics, 8(1), [e1002457]. https://doi.org/10.1371/journal.pgen.1002457