PACT and PKR: Turning on NF-
B in the Absence of Virus
Fulvio D'Acquisto, and
Sankar Ghosh
The authors are in the Section of Immunobiology and Department of Molecular Biophysics and Biochemistry, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. E-mail: sankar.ghosh{at}yale.edu
Abstract:
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-
B) 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-B by PKR and discuss three major unanswered questions. First, is PACT an alternative to dsRNA as a direct activator of the PKR-NF-B 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?
Citation:
F. D'Acquisto, S. Ghosh, PACT and PKR: Turning on NF-B in the Absence of Virus. Science's STKE (2001), http://stke.sciencemag.org/cgi/content/full/OC_sigtrans;2001/89/re1.
© 2001 American Association for the Advancement of Science
