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Die—but not just yet

The anti-apoptotic NF-B signal dominates before the pro-apoptotic eIF-2 signal. Donzé/Macmillan

Protein kinase R (PKR) pronounces a delayed death sentence on virus-infected cells, according to Olivier Donzé (Apotech Corporation, Epalinges, Switzerland), Nahum Sonenberg (McGill University, Montreal, Canada), and colleagues (Université de Genève, Switzerland). The delay may give time for the infected cells to signal to the immune system before the cells apoptose to kill the replicating virus.

Two signals downstream of PKR had been detected before: a kinase-independent activation of NF-B and a kinase-dependent inactivation of the translation factor eIF-2, leading to apoptosis. But the previous studies focused on one pathway at a time.

Donzé induced PKR production and saw that NF-B activation preceded eIF-2 phosphorylation by several hours. The same was true after virus infection. NF-B induced numerous downstream genes including several anti-apoptotic factors. Sure enough, cells lacking the NF-B response died more quickly.

Precedent exists for NF-B induction downstream of virus binding to a receptor. But activation of PKR's kinase activity, and thus phosphorylation of eIF-2, is delayed until later, when the virus starts replicating. The double-stranded RNA of the replicated virus activates PKR. Presumably eIF-2 phosphorylation inhibits the translation of anti-apoptotic mRNAs (such as those induced by NF-B), while sparing translation of the pro-apoptotic proteins that kill off the cell.

Reference:

Donzé, O., et al. 2004. EMBO J. 10.1038/sj.emboj.7600078.

William A. Wells

wellsw{at}rockefeller.edu

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This Article Full Text (PDF, 702K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Social Bookmarking                            What's this?