A non-canonical role of the p97 complex in RIG-I antiviral signaling

doi:10.15252/embj.201591888

	A non-canonical role of the p97 complex in RIG-I antiviral signaling
	Hao, Qian 1; Jiao, Shi 1; Shi, Zhubing 1; Li, Chuanchuan 1; Meng, Xia 1; Zhang, Zhen 1; Wang, Yanyan 1; Song, Xiaomin 1; Wang, Wenjia 1; Zhang, Rongguang 1; Zhao, Yun 1; Wong, Catherine C. L.1; Zhou, Zhaocai1,2
	2015-12-02
发表期刊	EMBO JOURNAL
ISSN	0261-4189
卷号	34 期号:23 页码:2903-2920
发表状态	已发表
DOI	10.15252/embj.201591888
摘要	RIG-I is a well-studied sensor of viral RNA that plays a key role in innate immunity. p97 regulates a variety of cellular events such as protein quality control, membrane reassembly, DNA repair, and the cell cycle. Here, we report a new role for p97 with Npl4-Ufd1 as its cofactor in reducing antiviral innate immune responses by facilitating proteasomal degradation of RIG-I. The p97 complex is able to directly bind both non-ubiquitinated RIG-I and the E3 ligase RNF125, promoting K48-linked ubiquitination of RIG-I at residue K181. Viral infection significantly strengthens the interaction between RIG-I and the p97 complex by a conformational change of RIG-I that exposes the CARDs and through K63-linked ubiquitination of these CARDs. Disruption of the p97 complex enhances RIG-I antiviral signaling. Consistently, administration of compounds targeting p97 ATPase activity was shown to inhibit viral replication and protect mice from vesicular stomatitis virus (VSV) infection. Overall, our study uncovered a previously unrecognized role for the p97 complex in protein ubiquitination and revealed the p97 complex as a potential drug target in antiviral therapy.
关键词	antiviral signaling mechanism p97-Npl4 RIG-I ubiquitination
收录类别	SCI
语种	英语
资助项目	Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences[2014KIP202]
WOS研究方向	Biochemistry & Molecular Biology ; Cell Biology
WOS类目	Biochemistry & Molecular Biology ; Cell Biology
WOS记录号	WOS:000367917600004
出版者	WILEY
WOS关键词	VALOSIN-CONTAINING PROTEIN ; AAA-ATPASE P97/VCP ; NF-KAPPA-B ; PATTERN-RECOGNITION RECEPTORS ; TUMOR-SUPPRESSOR CYLD ; E3 UBIQUITIN LIGASE ; TOLL-LIKE RECEPTOR ; INDUCIBLE GENE-I ; P97/VALOSIN-CONTAINING PROTEIN ; NEGATIVE REGULATION
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/2073
专题	生命科学与技术学院_特聘教授组_周兆才组
通讯作者	Wong, Catherine C. L.
作者单位	1.Chinese Acad Sci, Natl Ctr Prot Sci Shanghai, State Key Lab Cell Biol, Inst Biochem & Cell Biol,Shanghai Inst Biol Sci, Shanghai, Peoples R China 2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Hao, Qian,Jiao, Shi,Shi, Zhubing,et al. A non-canonical role of the p97 complex in RIG-I antiviral signaling[J]. EMBO JOURNAL,2015,34(23):2903-2920.
APA	Hao, Qian.,Jiao, Shi.,Shi, Zhubing.,Li, Chuanchuan.,Meng, Xia.,...&Zhou, Zhaocai.(2015).A non-canonical role of the p97 complex in RIG-I antiviral signaling.EMBO JOURNAL,34(23),2903-2920.
MLA	Hao, Qian,et al."A non-canonical role of the p97 complex in RIG-I antiviral signaling".EMBO JOURNAL 34.23(2015):2903-2920.