病毒诱导的 TRAF3/6 通过 cIAP1/2 的泛素化对于诱导干扰素-β（IFN-β）和细胞抗病毒反应是必不可少的。
Virus-triggered ubiquitination of TRAF3/6 by cIAP1/2 is essential for induction of interferon-beta (IFN-beta) and cellular antiviral response.
机构信息
College of Life Sciences, Wuhan University, Wuhan 430072, China.
College of Life Sciences, Wuhan University, Wuhan 430072, China.
出版信息
J Biol Chem. 2010 Mar 26;285(13):9470-9476. doi: 10.1074/jbc.M109.071043. Epub 2010 Jan 22.
Abstract
Viral infection causes activation of transcription factors NF-kappaB 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-kappaB 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.
摘要
病毒感染会导致转录因子 NF-κB 和 IRF3 的激活，它们共同诱导 I 型干扰素 (IFN) 和细胞抗病毒反应。在这里，我们表明，E3 泛素连接酶 cIAP1 和 cIAP2 的敲低显著抑制了病毒触发的 IRF3 和 NF-κB 的激活以及 IFN-β的诱导。cIAP1 和 cIAP2 的敲低也抑制了细胞质 dsRNA 触发的细胞抗病毒反应。内源性共免疫沉淀实验表明，病毒感染导致 cIAP1 和 cIAP2 募集到 TRAF3、TRAF6 和 VISA。此外，我们证明了 cIAP1 和 cIAP2 介导的病毒触发的 TRAF3 和 TRAF6 的泛素化。这些发现表明，cIAP1 和 cIAP2 触发的 TRAF3 和 TRAF6 的泛素化对于 I 型 IFN 的诱导和细胞抗病毒反应至关重要。
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