Interferon regulatory factor-3 is an in vivo target of DNA-PK Academic Article uri icon

Overview

MeSH Major

  • DNA-Binding Proteins
  • Protein-Serine-Threonine Kinases
  • Transcription Factors

abstract

  • 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-alpha and -beta 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.

publication date

  • March 5, 2002

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC122431

Digital Object Identifier (DOI)

  • 10.1073/pnas.052713899

PubMed ID

  • 11867762

Additional Document Info

start page

  • 2818

end page

  • 23

volume

  • 99

number

  • 5