Cell Signaling Technology

Translational Control: Regulation of eIF2

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Translational Control: Regulation of eIF2

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通路描述:

eIF2起始复合物整合了许多压力相关的信号来调节广泛和特定的mRNA翻译。在允许的情况下,eIF2和GTP还有Met-tRNA结合后形成三级复合物,这个复合物与40S核糖体亚基、eIF1、eIF1A、eIF5和 eIF3形成43S起始前复合体(pre-initiation complex,PIC)。这个43S PIC接着扫描整个mRNA UTR区寻找AUG起始位点。一旦识别到AUG密码子,eIF2将GTP水解成GDP,并从mRNA上解离下来。这使得60S核糖体亚基结合上来从而使多肽链延伸。要使eIF2起始另一轮的翻译,它所结合的GDP必须被换成GTP,这是由鸟嘌呤核苷酸交换因子(GEF)eIF2B催化完成的。这个步骤是被严密调控的,四个压力激活的激酶—PKR (dsRNA), PERK (内质网应激活化), GCN2 (氨基酸缺乏), 和HRI (亚铁血红素不足)对eIF2的磷酸化阻断了核苷酸的转换。eIF2-GDP的增加限制了三级复合物的获得,从而导致细胞内的蛋白合成减少,然而却增加了特定的压力相关的mRNA转录本的翻译,如转录因子ATF-4。

主要文献:

We would like to thank Carson Thoreen and Prof. David Sabatini, Whitehead Institute for Biomedical Research, MIT, Cambridge, MA, for reviewing this diagram.

created January 2002

revised November 2012

References