The double-strand RNA-dependent protein kinase PKR plays a significant role in a sustained ER stress-induced apoptosis
The double-strand RNA-dependent protein kinase PKR plays a significant role in a sustained ER stress-induced apoptosis
复制标题
DOI：
10.1016/j.febslet.2007.08.001
复制
发表时间：
2007-09-04
期刊：
影响因子：
3.5
通讯作者：
Bae, Yong-Soo
中科院分区：
文献类型：
--
作者：
Lee, Eun-Soo;Yoon, Cheol-Hee;Bae, Yong-Soo
持续的内质网应激导致细胞凋亡。然而，确切的机制仍有待阐明。在这里，我们证明了双链RNA依赖性蛋白激酶（PKR）参与ER应激介导的信号通路。ER应激迅速激活PKR，诱导eIF 2 α磷酸化，随后激活ATF 4/CHOP通路。ER-stress介导的eIF 2 alpha/ATF 4/CHOP信号传导和相关的细胞死亡被PKR敲低显著降低。我们还发现，PKR激活介导的PACT，其表达升高ER应激。这些结果表明，ER应激介导的eIF 2 α/ATF 4/CHOP/细胞死亡途径在一定程度上依赖于除PERK途径之外的PACT介导的PKR活化。(c)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Sustained ER stress leads to apoptosis. However, the exact mechanism still remains to be elucidated. Here, we demonstrate that the double strand RNA-dependent protein kinase (PKR) is involved in the ER stress-mediated signaling pathway. ER stress rapidly activated PKR, inducing the phosphorylation of eIF2 alpha, followed by the activation of the ATF4/CHOP pathway. ER-stress-mediated eIF2 alpha/ATF4/CHOP signaling and associated cell death was markedly reduced by PKR knockdown. We also found that PKR activation was mediated by PACT, the expression of which was elevated by ER-stress. These results indicate that the ER-stress-mediated eIF2 alpha/ATF4/CHOP/cell death pathway is, to some degree, dependent on PACT-mediated PKR activation apart from the PERK pathway. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.