DEAD盒解旋酶DDX3X是TANK结合激酶1依赖性先天免疫反应的关键组成部分。
The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response.
作者信息
Soulat Didier, Bürckstümmer Tilmann, Westermayer Sandra, Goncalves Adriana, Bauch Angela, Stefanovic Adrijana, Hantschel Oliver, Bennett Keiryn L, Decker Thomas, Superti-Furga Giulio
机构信息
Department of Infection Biology, Max F Perutz Laboratories, University of Vienna, Vienna, Austria.
出版信息
EMBO J. 2008 Aug 6;27(15):2135-46. doi: 10.1038/emboj.2008.126. Epub 2008 Jun 26.
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.
TANK结合激酶1（TBK1）对于响应病原体诱导I型干扰素（IFN）至关重要。我们鉴定出DEAD盒解旋酶DDX3X为TBK1的相互作用伴侣。TBK1和DDX3X在刺激IFN启动子的能力上具有协同作用，而RNA干扰介导的DDX3X表达降低导致IFN产生受损。染色质免疫沉淀表明，单核细胞增生李斯特菌感染后DDX3X被招募至IFN启动子，提示其转录作用机制。发现DDX3X在体外和体内均为TBK1的底物。DDX3X的磷酸化缺陷突变体在刺激IFN启动子的能力上无法与TBK1协同作用。总体而言，我们的数据表明DDX3X是TBK1的关键效应因子，是I型干扰素诱导所必需的。
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