The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway

doi:10.1371/journal.ppat.1007435

	The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway
	Zhang, Lele 1; Wei, Ning 2; Cui, Ye 1; Hong, Ze 2; Liu, Xing 3; Wang, Qiang 1; Li, Senlin 1; Liu, Heng 1; Yu, Huansha 1; Cai, Yanni 1; Wang, Quanyi 2; Zhu, Juanjuan 2; Meng, Wei 2; Chen, Zhengjun1,4 ; Wang, Chen 2
	2018-11
发表期刊	PLOS PATHOGENS (IF:5.5[JCR-2023],5.5[5-Year])
ISSN	1553-7366
卷号	14 期号:11
发表状态	已发表
DOI	10.1371/journal.ppat.1007435
摘要	Stimulator of interferon genes (STING) is critical for cytosolic DNA-triggered innate immunity. STING is modified by several types of polyubiquitin chains. Here, we report that the deubiquitinase CYLD sustains STING signaling by stabilizing the STING protein. CYLD deficiency promoted the K48-linked polyubiquitination and degradation of STING, attenuating the induction of IRF3-responsive genes after HSV-1 infection or the transfection of DNA ligands. Additionally, CYLD knockout mice were more susceptible to HSV-1 infection than their wild-type (WT) littermates. Mechanistically, STING translocated from the ER to the Golgi upon HSV-1 stimulation; CYLD partially accumulated with STING and interacted selectively with K48-linked polyubiquitin chains on STING, specifically removing the K48-linked polyubiquitin chains from STING and ultimately boosting the innate antiviral response. Our study reveals that CYLD is a novel checkpoint in the cGAS-STING signaling pathway and sheds new light on the dynamic regulation of STING activity by ubiquitination.
收录类别	SCI ; SCIE
语种	英语
资助项目	National New Drug Innovation Major Project of China[2017ZX09309027]
WOS研究方向	Microbiology ; Parasitology ; Virology
WOS类目	Microbiology ; Parasitology ; Virology
WOS记录号	WOS:000451831800034
出版者	PUBLIC LIBRARY SCIENCE
WOS关键词	CYCLIC GMP-AMP ; TUMOR-SUPPRESSOR CYLD ; CYTOSOLIC DNA SENSOR ; NF-KAPPA-B ; INNATE ; ADAPTER ; KINASE ; 2ND-MESSENGER ; RECOGNITION ; ENZYME
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/29038
专题	生命科学与技术学院_特聘教授组_陈正军组
通讯作者	Chen, Zhengjun; Wang, Chen
作者单位	1.Univ Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Chinese Acad Sci, State Key Lab Cell Biol,CAS Ctr Excellence Mol Ce, Shanghai, Peoples R China 2.China Pharmaceut Univ, Sch Life Sci & Technol, State Key Lab Nat Med, 639 Longmian Ave, Nanjing, Jiangsu, Peoples R China 3.Chinese Acad Sci, Inst Pasteur Shanghai, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China 4.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Lele,Wei, Ning,Cui, Ye,et al. The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway[J]. PLOS PATHOGENS,2018,14(11).
APA	Zhang, Lele.,Wei, Ning.,Cui, Ye.,Hong, Ze.,Liu, Xing.,...&Wang, Chen.(2018).The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway.PLOS PATHOGENS,14(11).
MLA	Zhang, Lele,et al."The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway".PLOS PATHOGENS 14.11(2018).