en
Scientific article
English

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

Published inEMBO journal, vol. 23, no. 3, p. 564-571
Publication date2004
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
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. 564–571. doi: 10.1038/sj.emboj.7600078
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Article (Published version)
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ISSN of the journal0261-4189
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