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The protein kinase PKR: a molecular clock that sequentially activates survival and death programs

Deng, Jing
Sladek, Robert
Sonenberg, Nahum
Published in EMBO journal. 2004, vol. 23, no. 3, p. 564-71
Abstract 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-kappaB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF-2alpha. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions.
Keywords AnimalsApoptosis/physiologyCell Survival/physiologyEukaryotic Initiation Factor-2/metabolismMiceNF-kappa B/metabolismNIH 3T3 CellsPhosphorylationSignal Transduction/physiologyEIF-2 Kinase/metabolism
PMID: 14749731
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DONZE, Olivier et al. The protein kinase PKR: a molecular clock that sequentially activates survival and death programs. In: EMBO journal, 2004, vol. 23, n° 3, p. 564-71. doi: 10.1038/sj.emboj.7600078 https://archive-ouverte.unige.ch/unige:4659

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Deposited on : 2009-12-11

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