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

The DEAD-box helicase DDX3X is a critical component of the TANK-binding kinase 1-dependent innate immune response.
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DOI:
10.1038/emboj.2008.126
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发表时间:
2008-08-06
期刊:
影响因子:
11.4
通讯作者:
Superti-Furga, Giulio
Superti-Furga, Giulio
中科院分区:
生物学1区
文献类型:
--
作者:
Soulat, Didier;Buerckstuemmer, Tilmann;Westermayer, Sandra;Goncalves, Adriana;Bauch, Angela;Stefanovic, Adrijana;Hantschel, Oliver;Bennett, Keiryn L.;Decker, Thomas;Superti-Furga, Giulio

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TANK-BINDING KEK1(TANK-BINDING KEK1)在诱导I型干扰素对病原体的应答中起着重要的作用。我们确定死盒解旋酶DDX3X是TBK1的相互作用伙伴。TBK1和DDX3X在刺激干扰素启动子的能力方面具有协同作用,而RNAi介导的DDX3X表达的降低导致干扰素的产生受到抑制。染色质免疫沉淀表明,DDX3X在感染单核细胞增多性李斯特菌后被募集到干扰素启动子上,这可能是一种转录作用机制。在体外和体内实验中发现DDX3X是一种TBK1底物。DDX3X的磷酸化缺陷突变体不能与TBK1协同刺激干扰素启动子。总体而言,我们的数据表明,DDX3X是TBK1的关键效应器,是诱导I型干扰素所必需的。
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.
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