SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation

被引：72

作者：

Ran, Yong ^{[1
]}

Liu, Tian-Tian ^{[1
]}

Zhou, Qian ^{[1
]}

Li, Shu ^{[1
]}

Mao, Ai-Ping ^{[1
]}

Li, Ying ^{[1
]}

Liu, Li-Juan ^{[1
]}

Cheng, Jin-Ke ^{[2
]}

Shu, Hong-Bing ^{[1
]}

机构：

[1] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China

[2] Shanghai Jiao Tong Univ, Sch Med, Dept Biochem & Mol Cell Biol, Shanghai 200025, Peoples R China

来源：

JOURNAL OF MOLECULAR CELL BIOLOGY | 2011年 / 3卷 / 05期

基金：

中国国家自然科学基金;

关键词：

SENP2; IRF3; deSUMOylation; ubiquitination; innate immunity; INDUCIBLE GENE-I; NF-KAPPA-B; IFN-BETA; INNATE IMMUNITY; PROTEASE; SUMO; INTERFERON; ACTIVATION; ADAPTER; LIGASE;

D O I：

10.1093/jmcb/mjr020

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Transcription factor IRF3-mediated type I interferon induction is essential for antiviral innate immunity. We identified the deSUMOylating enzyme Sentrin/SUMO-specific protease (SENP) 2 as a negative regulator of virus-triggered IFN-beta induction. Overexpression of SENP2 caused IRF3 deSUMOylation, K48-linked ubiquitination, and degradation, whereas depletion of SENP2 had opposite effects. Both the SUMOylation and K48-linked ubiquitination of IRF3 occurred at lysines 70 and 87, and these processes are competitive. The level of virus-triggered IFN-beta was markedly up-regulated and viral replication was reduced in SENP2-deficient cells comparing with wild-type controls. Our findings suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation, and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity.

引用

页码：283 / 292

页数：10

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