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

Donze, Olivier; Deng, Jing; Curran, Joseph; Sladek, Robert; Picard, Didier; Sonenberg, Nahum

doi:10.1038/sj.emboj.7600078

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Title		The protein kinase PKR: a molecular clock that sequentially activates survival and death programs
Authors		Donze, Olivier Deng, Jing Curran, Joseph Sladek, Robert Picard, Didier 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		Animals — Apoptosis/physiology — Cell Survival/physiology — Eukaryotic Initiation Factor-2/metabolism — Mice — NF-kappa B/metabolism — NIH 3T3 Cells — Phosphorylation — Signal Transduction/physiology — EIF-2 Kinase/metabolism
Identifiers		DOI: 10.1038/sj.emboj.7600078 PMID: 14749731
Full text		Article (Published version) (261 Kb) - Limited access to UNIGE
Structures		Faculté des sciences / Section de biologie / Département de biologie cellulaire Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire
Citation (ISO format)		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