The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response

• Published in: The EMBO journal Vol. 27; no. 15; pp. 2135 - 2146
• Main Authors: Soulat, Didier, Bürckstümmer, Tilmann, Westermayer, Sandra, Goncalves, Adriana, Bauch, Angela, Stefanovic, Adrijana, Hantschel, Oliver, Bennett, Keiryn L, Decker, Thomas, Superti-Furga, Giulio
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 06.08.2008; Nature Publishing Group UK; Springer Nature B.V; Nature Publishing Group
• Subjects: Amino Acid Sequence; Cell Line; Chromatin; DDX3X; DEAD-box RNA Helicases - genetics; DEAD-box RNA Helicases - metabolism; DEAD-box RNA Helicases - physiology; EMBO19; EMBO37; Genetics; Humans; Immune response; Immunity, Innate; innate immunity; interferon; Interferon Type I - biosynthesis; Interferon Type I - genetics; Interferon Type I - immunology; Kinases; Listeria monocytogenes; Listeria monocytogenes - physiology; Listeriosis - immunology; Listeriosis - metabolism; Models, Molecular; Molecular biology; Molecular Sequence Data; Mutation; Pathogens; Phosphorylation; Promoter Regions, Genetic; Protein Binding; Protein Serine-Threonine Kinases - metabolism; Protein Serine-Threonine Kinases - physiology; TBK1; DDX3X; TBK1; innate immunity; interferon; phosphorylation
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.1038/emboj.2008.126

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.