Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade.
Rheb Inhibits Protein Synthesis by Activating the PERK-eIF2α Signaling Cascade.
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DOI：
10.1016/j.celrep.2015.01.014
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发表时间：
2015-02-10
期刊：
影响因子：
8.8
通讯作者：
Subramaniam S
中科院分区：
文献类型：
--
作者：
Tyagi R;Shahani N;Gorgen L;Ferretti M;Pryor W;Chen PY;Swarnkar S;Worley PF;Karbstein K;Snyder SH;Subramaniam S
Rheb是一种普遍存在的小GTPase，众所周知，它可以结合并激活mTOR，从而增加蛋白质合成。蛋白质合成的抑制也受生理调节。因此，在细胞应激下，未折叠的蛋白质反应系统导致起始因子eIF2α的磷酸化和蛋白质合成的停滞。我们现在证明Rheb通过蛋白激酶样内质网激酶（PERK）增强eIF2α的磷酸化来抑制蛋白质合成的主要作用。Rheb的刺激和抑制作用之间的相互作用可能使细胞能够调节蛋白质合成以响应不同的环境压力。
Rheb, a ubiquitous small GTPase, is well known to bind and activate mTOR, which augments protein synthesis. Inhibition of protein synthesis is also physiologically regulated. Thus, with cell stress the unfolded protein response system leads to phosphorylation of the initiation factor eIF2α and arrest of protein synthesis. We now demonstrate a major role for Rheb in inhibiting protein synthesis through enhancing the phosphorylation of eIF2α by protein kinase-like endoplasmic reticulum kinase (PERK). Interplay between the stimulatory and inhibitory roles of Rheb may enable cells to modulate protein synthesis in response to varying environmental stresses.