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FEBS Lett. 2007 Sep 4;581(22):4325-32. Epub 2007 Aug 14.

The double-strand RNA-dependent protein kinase PKR plays a significant role in a sustained ER stress-induced apoptosis.

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  • 1Department of Biological Science, Sungkyunkwan University, Cheoncheon-dong 300, Jangan-gu, Suwon, Gyeonggi-do 440-746, South Korea.


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 eIF2alpha, followed by the activation of the ATF4/CHOP pathway. ER-stress-mediated eIF2alpha/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 eIF2alpha/ATF4/CHOP/cell death pathway is, to some degree, dependent on PACT-mediated PKR activation apart from the PERK pathway.

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