title: The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response.
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.
authors.affiliation: Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.
authors.forename: Didier
authors.initials: D
authors.lastname: Soulat
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bürckstümmer
authors.forename: Sandra
authors.initials: S
authors.lastname: Westermayer
authors.forename: Adriana
authors.initials: A
authors.lastname: Goncalves
authors.forename: Angela
authors.initials: A
authors.lastname: Bauch
authors.forename: Adrijana
authors.initials: A
authors.lastname: Stefanovic
authors.forename: Oliver
authors.initials: O
authors.lastname: Hantschel
authors.forename: Keiryn L
authors.initials: KL
authors.lastname: Bennett
authors.forename: Thomas
authors.initials: T
authors.lastname: Decker
authors.forename: Giulio
authors.initials: G
authors.lastname: Superti-Furga
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008089:Listeria monocytogenes / Q000502:physiology; D008088:Listeriosis / Q000276:immunology / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D007370:Interferon Type I; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases