The DEAD-box Helicase DDX3X Is a Critical Component of the TANK-binding Kinase 1-dependent Innate Immune Response

EMBO J. 2008 Aug 6;27(15):2135-46. doi: 10.1038/emboj.2008.126. Epub 2008 Jun 26.

Abstract

TANK-binding kinase 1 (TBK1) is of central importance for the induction of type-I interferon (IFN) in response to pathogens. We identified the DEAD-box helicase DDX3X as an interaction partner of TBK1. TBK1 and DDX3X acted synergistically in their ability to stimulate the IFN promoter, whereas RNAi-mediated reduction of DDX3X expression led to an impairment of IFN production. Chromatin immunoprecipitation indicated that DDX3X is recruited to the IFN promoter upon infection with Listeria monocytogenes, suggesting a transcriptional mechanism of action. DDX3X was found to be a TBK1 substrate in vitro and in vivo. Phosphorylation-deficient mutants of DDX3X failed to synergize with TBK1 in their ability to stimulate the IFN promoter. Overall, our data imply that DDX3X is a critical effector of TBK1 that is necessary for type I IFN induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism
  • DEAD-box RNA Helicases / physiology*
  • Humans
  • Immunity, Innate*
  • Interferon Type I / biosynthesis
  • Interferon Type I / genetics
  • Interferon Type I / immunology*
  • Listeria monocytogenes / physiology
  • Listeriosis / immunology
  • Listeriosis / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Phosphorylation
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • Interferon Type I
  • Protein-Serine-Threonine Kinases
  • TBK1 protein, human
  • DDX3X protein, human
  • DEAD-box RNA Helicases