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


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.

SUBMITTER: Donze O 

PROVIDER: S-EPMC1271809 | biostudies-literature | 2004 Feb

REPOSITORIES: biostudies-literature

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

Donzé Olivier O   Deng Jing J   Curran Joseph J   Sladek Robert R   Picard Didier D   Sonenberg Nahum N  

The EMBO journal 20040129 3


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 proapo  ...[more]

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