The anti-apoptotic NF-κB signal dominates before the pro-apoptotic eIF-2α 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-κB and a kinase-dependent inactivation of the translation factor eIF-2α, leading to apoptosis. But the previous studies focused on one pathway at a time.

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

The Rockefeller University Press
2004
The Rockefeller University Press
2004
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