NEMO-IKK beta Are Essential for IRF3 and NF-kappa B Activation in the   cGAS-STING Pathway

doi:10.4049/jimmunol.1700699

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	NEMO-IKK beta Are Essential for IRF3 and NF-kappa B Activation in the cGAS-STING Pathway
	Fang, Run ; Wang, Chenguang ; Jiang, Qifei ; Lv, Mengze ; Gao, Pengfei ; Yu, Xiaoyu ; Mu, Ping ; Zhang, Rui ; Bi, Sheng ; Feng, Ji-Ming ; Jiang, Zhengfan
刊名	JOURNAL OF IMMUNOLOGY
	2017
关键词	UBIQUITIN-BINDING PROTEINS I INTERFERON INDUCTION INNATE IMMUNE-RESPONSE CYCLIC GMP-AMP CYTOSOLIC-DNA ADAPTER PROTEIN NUCLEIC-ACIDS RIG-I KINASE VIRUS
DOI	10.4049/jimmunol.1700699
英文摘要	Cytosolic dsDNA activates the cyclic GMP-AMP synthase (cGAS)-stimulator of IFN genes (STING) pathway to produce cytokines, including type I IFNs. The roles of many critical proteins, including NEMO, IKK beta, and TBK1, in this pathway are unclear because of the lack of an appropriate system to study. In this article, we report that lower FBS concentrations in culture medium conferred high sensitivities to dsDNA in otherwise unresponsive cells, whereas higher FBS levels abrogated this sensitivity. Based on this finding, we demonstrated genetically that NEMO was critically involved in the cGAS-STING pathway. Cytosolic DNA activated TRIM32 and TRIM56 to synthesize ubiquitin chains that bound NEMO and subsequently activated IKK beta. Activated IKK beta, but not IKK alpha, was required for TBK1 and NF-kappa B activation. In contrast, TBK1 was reciprocally required for NF-kappa B activation, probably by directly phosphorylating IKK beta. Thus, our findings identified a unique innate immune activation cascade in which TBK1-IKK beta formed a positive feedback loop to assure robust cytokine production during cGAS-STING activation.; Chinese Ministry of Science and Technology [2014CB542600, 2015CB943203]; China Natural Science Foundation [31230023, 91129000, 81621001]; SCI(E); ARTICLE; 9; 3222-3233; 199
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/484552]
专题	生命科学学院
推荐引用方式 GB/T 7714	Fang, Run,Wang, Chenguang,Jiang, Qifei,et al. NEMO-IKK beta Are Essential for IRF3 and NF-kappa B Activation in the cGAS-STING Pathway[J]. JOURNAL OF IMMUNOLOGY,2017.
APA	Fang, Run.,Wang, Chenguang.,Jiang, Qifei.,Lv, Mengze.,Gao, Pengfei.,...&Jiang, Zhengfan.(2017).NEMO-IKK beta Are Essential for IRF3 and NF-kappa B Activation in the cGAS-STING Pathway.JOURNAL OF IMMUNOLOGY.
MLA	Fang, Run,et al."NEMO-IKK beta Are Essential for IRF3 and NF-kappa B Activation in the cGAS-STING Pathway".JOURNAL OF IMMUNOLOGY (2017).