Virus-triggered Ubiquitination of TRAF3/6 by cIAP1/2 Is Essential for Induction of Interferon-β (IFN-β) and Cellular Antiviral Response

被引:115
作者
Mao, Ai-Ping [1 ]
Li, Shu [1 ]
Zhong, Bo [1 ]
Li, Ying [1 ]
Yan, Jie [1 ]
Li, Qi [1 ]
Teng, Chengwen [1 ]
Shu, Hong-Bing [1 ]
机构
[1] Wuhan Univ, Coll Life Sci, Wuhan 430072, Peoples R China
基金
中国国家自然科学基金;
关键词
NF-KAPPA-B; NEGATIVE REGULATION; SIGNALING COMPLEX; ADAPTER PROTEIN; ACTIVATION PATHWAYS; I INTERFERON; LIGASE; INNATE; KINASE; TRANSDUCTION;
D O I
10.1074/jbc.M109.071043
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Viral infection causes activation of transcription factors NF-kappa B and IRF3, which collaborate to induce type I interferons (IFNs) and cellular antiviral response. Here we show that knockdown of the E3 ubiquitin ligases cIAP1 and cIAP2 markedly inhibited virus-triggered activation of IRF3 and NF-kappa B as well as IFN-beta induction. Knockdown of cIAP1 and cIAP2 also inhibited cytoplasmic dsRNA-triggered cellular antiviral response. Endogenous coimmunoprecipitation experiments indicated that viral infection caused recruitment of cIAP1 and cIAP2 to TRAF3, TRAF6, and VISA. Furthermore, we demonstrated that cIAP1- and cIAP2-mediated virus-triggered ubiquitination of TRAF3 and TRAF6. These findings suggest that virus-triggered ubiquitination of TRAF3 and TRAF6 by cIAP1 and cIAP2 is essential for type I IFN induction and cellular antiviral response.
引用
收藏
页码:9470 / 9476
页数:7
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