Positive Regulation of Interferon Regulatory Factor 3 Activation by Herc5 via ISG15 Modification

	Positive Regulation of Interferon Regulatory Factor 3 Activation by Herc5 via ISG15 Modification
	Shi, HX; Yang, K; Liu, X; Liu, XY; Wei, B; Shan, YF; Zhu, LH; Wang, C
刊名	MOLECULAR AND CELLULAR BIOLOGY
	2010
卷号	30 期号:10 页码:2424-2436
通讯作者	Wang, C (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,cwang01@sibs.ac.cn
英文摘要	Virus infection induces host antiviral responses, including induction of type I interferons. Transcription factor interferon regulatory factor 3 (IRF3) plays a pivotal role and is tightly regulated in this process. Here, we identify HERC5 (HECT domain and RLD 5) as a specific binding protein of IRF3 by immunoprecipitation. Ectopic expression or knockdown of HERC5 could, respectively, enhance or impair IRF3-mediated gene expression. Mechanistically, HERC5 catalyzes the conjugation of ubiquitin-like protein ISG15 onto IRF3 (Lys193, -360, and -366), thus attenuating the interaction between Pin1 and IRF3, resulting in sustained IRF3 activation. In contrast to results for wild-type IRF3, the mutant IRF3(K193,360,366R) interacts tightly with Pin1, is highly polyubiquitinated, and becomes less stable upon Sendai virus (SeV) infection. Consistently, host antiviral responses are obviously boosted or crippled in the presence or absence of HERC5, respectively. Collectively, this study characterizes HERC5 as a positive regulator of innate antiviral responses. It sustains IRF3 activation via a novel posttranslational modification, ISGylation.
学科主题	Biochemistry & Molecular Biology; Cell Biology
类目[WOS]	Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]	INNATE ANTIVIRAL RESPONSE ; TOLL-LIKE RECEPTOR ; NF-KAPPA-B ; UBIQUITIN-LIKE PROTEIN ; RIG-I ; NEGATIVE REGULATION ; IMMUNE-RESPONSE ; ADAPTER PROTEIN ; VIRUS ; PATHWAY
收录类别	SCI
语种	英语
WOS记录号	WOS:000277040900011
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/1064]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Shi, HX,Yang, K,Liu, X,et al. Positive Regulation of Interferon Regulatory Factor 3 Activation by Herc5 via ISG15 Modification[J]. MOLECULAR AND CELLULAR BIOLOGY,2010,30(10):2424-2436.
APA	Shi, HX.,Yang, K.,Liu, X.,Liu, XY.,Wei, B.,...&Wang, C.(2010).Positive Regulation of Interferon Regulatory Factor 3 Activation by Herc5 via ISG15 Modification.MOLECULAR AND CELLULAR BIOLOGY,30(10),2424-2436.
MLA	Shi, HX,et al."Positive Regulation of Interferon Regulatory Factor 3 Activation by Herc5 via ISG15 Modification".MOLECULAR AND CELLULAR BIOLOGY 30.10(2010):2424-2436.