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The protein kinase PKR: a molecular clock that sequentially activates survival and death programs
Author(s) -
Donzé Olivier,
Deng Jing,
Curran Joseph,
Sladek Robert,
Picard Didier,
Sonenberg Nahum
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600078
Subject(s) - biology , protein kinase r , protein kinase a , microbiology and biotechnology , kinase , programmed cell death , mitogen activated protein kinase kinase , apoptosis , cancer research , genetics
Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The interferon‐induced protein kinase PKR acts as a molecular clock by using catalysis‐dependent and ‐independent activities to temporally induce cell survival prior to cell death. We show that the proapoptotic protein PKR surprisingly activates a survival pathway, which is mediated by NF‐κB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF‐2α. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions.