The protein kinase PKR: a molecular clock that sequentially activates survival and death programs.
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.
Donzé
Olivier
O
Département de Biologie Cellulaire, Université de Genève, Sciences III, Genève, Switzerland. odonze@apotech.ch
Deng
Jing
J
Curran
Joseph
J
Sladek
Robert
R
Picard
Didier
D
Sonenberg
Nahum
N
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D015398:Signal Transduction / Q000502:physiology*; D019892:eIF-2 Kinase / Q000378:metabolism*
D015852:Eukaryotic Initiation Factor-2; D016328:NF-kappa B; D019892:eIF-2 Kinase