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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
PLoS genetics | 2012

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.

Pubmed ID: 22253608

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Associated grants

  • Agency: NICHD NIH HHS, United States
    Id: 2 T32 HD007312
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK032520
  • Agency: NIA NIH HHS, United States
    Id: R01 AG030323
  • Agency: NICHD NIH HHS, United States
    Id: 2 T32 HD007439
  • Agency: NICHD NIH HHS, United States
    Id: R01 HD037267
  • Agency: NICHD NIH HHS, United States
    Id: HD37267
  • Agency: NICHD NIH HHS, United States
    Id: R37 HD037267
  • Agency: NIA NIH HHS, United States
    Id: AG30323
  • Agency: NIDDK NIH HHS, United States
    Id: DK32520
  • Agency: NICHD NIH HHS, United States
    Id: T32 HD007312
  • Agency: NIDDK NIH HHS, United States
    Id: U24 DK093000
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM046779
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK067493
  • Agency: NICHD NIH HHS, United States
    Id: T32 HD007439
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK080756
  • Agency: NIDDK NIH HHS, United States
    Id: DK80756

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Gene Expression Omnibus (GEO) (tool)

RRID:SCR_007303

Functional genomics data repository supporting MIAME-compliant data submissions. Includes microarray-based experiments measuring the abundance of mRNA, genomic DNA, and protein molecules, as well as non-array-based technologies such as serial analysis of gene expression (SAGE) and mass spectrometry proteomic technology. Array- and sequence-based data are accepted. Collection of curated gene expression DataSets, as well as original Series and Platform records. The database can be searched using keywords, organism, DataSet type and authors. DataSet records contain additional resources including cluster tools and differential expression queries.

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University of Massachusetts; Massachusetts; USA (tool)

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Hep-G2 (tool)

RRID:CVCL_0027

Cell line Hep-G2 is a Cancer cell line with a species of origin Homo sapiens (Human)

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