The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response.
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.
Soulat
Didier
D
Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.
Bürckstümmer
Tilmann
T
Westermayer
Sandra
S
Goncalves
Adriana
A
Bauch
Angela
A
Stefanovic
Adrijana
A
Hantschel
Oliver
O
Bennett
Keiryn L
KL
Decker
Thomas
T
Superti-Furga
Giulio
G
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*
D007370:Interferon Type I; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; C119332:DDX3X protein, human; D053487:DEAD-box RNA Helicases