Eukaryotic Initiation Factor 2 Phosphorylation and Translational Control in Metabolism
Eukaryotic Initiation Factor 2 Phosphorylation and Translational Control in Metabolism
复制标题
代谢中的真核启动因子 2 磷酸化和转译控制
DOI：
10.3945/an.112.002113
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发表时间：
2012-05-01
影响因子：
9.3
通讯作者：
Wek, Ronald C.
中科院分区：
文献类型：
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作者：
Baird, Thomas D.;Wek, Ronald C.
mRNA 翻译的调节是将细胞环境的变化与整体蛋白质合成速率相结合的快速有效的方法。为了应对应激，例如营养缺乏和内质网中错误折叠蛋白的积累，真核起始因子 2 的 α 亚基（elF2 α 类似于 P）的磷酸化会减少一般翻译起始，同时促进选定转录物的优先翻译，例如编码激活转录因子 4 (ATF4) 的转录物，ATF4 是受整合应激反应 (ISR) 影响的基因的转录激活因子。在这篇综述中，我们重点介绍了营养应激调节的翻译控制过程，重点是与 P 类似的 elF2 α 触发的事件，并描述了真核起始因子 2 激酶家族以及每种激酶感知不同应激的机制。然后我们解决 3 个问题。首先，与 P 类似的 elF2 α 赋予选择性 mRNA 优先翻译的机制是什么？ISR 诱导的基因表达的后果是什么？其次，某些应激可以通过哪些分子过程来差异性地激活 eF2 α，类似于 P 和 ATF4 的表达？我们要解决的第三个问题是ISR和其他应激反应途径之间的交叉调节模式是什么，例如雷帕霉素的未折叠蛋白反应和哺乳动物靶标，以及这些调节方案如何提供针对特定应激的基因表达程序？这篇综述重点介绍了这些研究领域的最新进展，强调了与 P 和 ISR 相似的 elF2 α 如何影响代谢健康和疾病。副词。营养。 3:307-321，2012 年。
Regulation of mRNA translation is a rapid and effective means to couple changes in the cellular environment with global rates of protein synthesis. In response to stresses, such as nutrient deprivation and accumulation of misfolded proteins in the endoplasmic reticulum, phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (elF2 alpha similar to P) reduces general translation initiation while facilitating the preferential translation of select transcripts, such as that encoding activating transcription factor 4 (ATF4), a transcriptional activator of genes subject to the integrated stress response (ISR). In this review, we highlight the translational control processes regulated by nutritional stress, with an emphasis on the events triggered by elF2 alpha similar to P, and describe the family of eukaryotic initiation factor 2 kinases and the mechanisms by which each sense different stresses. We then address 3 questions. First, what are the mechanisms by which elF2 alpha similar to P confers preferential translation on select mRNA and what are the consequences of the gene expression induced by the ISR? Second, what are the molecular processes by which certain stresses can differentially activate elF2 alpha similar to P and ATF4 expression? The third question we address is what are the modes of cross-regulation between the ISR and other stress response pathways, such as the unfolded protein response and mammalian target of rapamycin, and how do these regulatory schemes provide for gene expression programs that are tailored for specific stresses? This review highlights recent advances in each of these areas of research, emphasizing how elF2 alpha similar to P and the ISR can affect metabolic health and disease. Adv. Nutr. 3:307-321, 2012.