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The double‐strand RNA‐dependent protein kinase PKR plays a significant role in a sustained ER stress‐induced apoptosis
Author(s) -
Lee Eun-Soo,
Yoon Cheol-Hee,
Kim Yeon-Soo,
Bae Yong-Soo
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.08.001
Subject(s) - protein kinase r , atf4 , eif 2 kinase , unfolded protein response , chop , apoptosis , microbiology and biotechnology , gene knockdown , kinase , programmed cell death , signal transduction , integrated stress response , phosphorylation , eif2 , protein kinase a , translation (biology) , chemistry , biology , cancer research , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , biochemistry , messenger rna , gene
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 eIF2α, followed by the activation of the ATF4/CHOP pathway. ER‐stress‐mediated eIF2α/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 eIF2α/ATF4/CHOP/cell death pathway is, to some degree, dependent on PACT‐mediated PKR activation apart from the PERK pathway.