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Interferon regulatory factor-3 is an in vivo target of DNA-PK

  • Alla Y. Karpova
  • Maren Trost
  • John M. Murray
  • Lewis C. Cantley
  • Peter M. Howley
The National Academy of Sciences
Publication Date
Feb 26, 2002
  • Biology
  • Ecology
  • Geography


Eukaryotic cells have evolved complex signaling networks to sense environmental stress and to repair stress-induced damage. IFN regulatory factor-3 (IRF-3) is a transcription factor that plays a central role in the host response to viral infection. Although the main activity of IRF-3 characterized to date has been its role in the induction of IFN-α and -β after virus infection, recent evidence indicates additional roles for IRF-3 in the response to DNA damage and in virus-induced apoptosis. Here we identify IRF-3 as the first in vivo target for DNA-dependent protein kinase (DNA-PK). Phosphorylation of IRF-3 by DNA-PK after virus infection results in its nuclear retention and delayed proteolysis. These results expand the known roles of DNA-PK and provide a functional link between the cellular machineries that regulate the innate immune response and that sense and respond to DNA damage. As such this study contributes to a more integrated view of the cellular responses to various cellular stress signals.

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