PACT and PKR: turning on NF-kappa B in the absence of virus.
Double-stranded RNA (dsRNA)-dependent protein kinase R (PKR) has been generally thought to be solely regulated by dsRNA, an intermediate in the replication of many viruses. However, the notion that PKR acts solely as a sensor for viral infection has been challenged by recent findings that alteration of PKR activity has effects on cellular growth and by the discovery of a virus-independent activator of PKR, a cellular protein called PACT (PKR-activating protein). The activation of the transcription factor nuclear factor kappa B (NF-kappaB) by PKR has been shown to account for the host antiviral response. We summarize the most recent findings on the molecular mechanisms leading to the activation of NF-kappaB by PKR and discuss three major unanswered questions. First, is PACT an alternative to dsRNA as a direct activator of the PKR-NF-kappaB pathway? Second, how is PACT itself activated and targeted to PKR? And third, what are the biological functions of PKR in the absence of viral infection?
D'Acquisto
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Section of Immunobiology, Department of Molecular Biophysics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. sankar.ghosh@yale.edu
Ghosh
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D000818:Animals; D017209:Apoptosis / Q000276:immunology / Q000502:physiology; D002352:Carrier Proteins / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins / Q000502:physiology*; D014780:Viruses / Q000201:enzymology*; D019892:eIF-2 Kinase / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D016328:NF-kappa B; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D019892:eIF-2 Kinase