Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance
Cytoplasmic Polyadenylation Element Binding Protein Deficiency Stimulates PTEN and Stat3 mRNA Translation and Induces Hepatic Insulin Resistance
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DOI：
10.1371/journal.pgen.1002457
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发表时间：
2012-01-01
期刊：
影响因子：
4.5
通讯作者：
Richter, Joel D.
中科院分区：
文献类型：
--
作者：
Alexandrov, Ilya M.;Ivshina, Maria;Richter, Joel D.
胞质多聚腺苷酸化元件结合蛋白CPEB 1（CPEB）调节生殖细胞发育、突触可塑性和细胞衰老。对CPEB调控的mRNA的微阵列分析意外地显示，几种编码的蛋白质参与胰岛素信号传导。对Cpeb1基因敲除小鼠的研究显示，胰岛素作用的两种特定负调节因子PTEN和Stat3的表达异常增加。CPEB缺陷小鼠肝脏中胰岛素信号转导Akt减弱，表明它们可能在调节葡萄糖稳态方面存在缺陷。事实上，当Cpeb1基因敲除小鼠被喂食高脂肪饮食时，它们的肝脏变得对胰岛素具有抵抗性。对消耗CPEB的人肝细胞系HepG2细胞的分析表明，该蛋白质直接调节PTEN和Stat3 mRNA的翻译。我们的研究结果表明，CPEB调控的翻译是参与胰岛素信号转导的关键过程。
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.