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

作者：Didier Soulat, Tilmann Bürckstümmer, Sandra Westermayer, Adriana Gonçalves, Angela Bauch, Adrijana Stefanovic, Oliver D. Hantschel, Keiryn L. Bennett, Thomas Decker, Giulio Superti‐Furga · 发表于：The EMBO Journal · 年份：2008 · DOI：10.1038/emboj.2008.126 · 被引用次数：330 · 研究领域：interferon and immune responses、Cytokine Signaling Pathways and Interactions、RNA regulation and disease

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.