Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3
Negative feedback regulation of cellular antiviral signaling by RBCK1-mediated degradation of IRF3
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DOI：
10.1038/cr.2008.277
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发表时间：
2008-11-01
期刊：
影响因子：
44.1
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Zhang, Min;Tian, Yang;Shu, Hong-Bing
病毒感染导致宿主细胞产生I型干扰素（IFN），其在病毒清除中起关键作用。先前的研究已经证明，转录因子干扰素调节因子（IRF）3的激活对于病毒触发的I型IFN的诱导是必不可少的。在这里，我们表明，E3泛素连接酶RBCC蛋白与PKC 1（RBCK 1）相互作用，催化IRF3的泛素化和降解。RBCK 1的过表达负性调节仙台病毒触发的I型IFN的诱导，而RBCK 1的敲低则具有相反的作用。空斑试验一致表明，RBCK 1负调节细胞的抗病毒反应。此外，病毒感染导致RBCK 1的诱导和随后的IRF 3降解。这些发现表明，细胞的抗病毒反应是由一个负反馈调节机制，涉及RBCK 1介导的泛素化和降解的IRF3。
Viral infection causes host cells to produce type I interferons (IFNs), which are critically involved in viral clearance. Previous studies have demonstrated that activation of the transcription factor interferon regulatory factor (IRF) 3 is essential for virus-triggered induction of type I IFNs. Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. Overexpression of RBCK1 negatively regulates Sendai virus-triggered induction of type I IFNs, while knockdown of RBCK1 has the opposite effect. Plaque assays consistently demonstrate that RBCK1 negatively regulates the cellular antiviral response. Furthermore, viral infection leads to induction of RBCK1 and subsequent degradation of IRF3. These findings suggest that the cellular antiviral response is controlled by a negative feedback regulatory mechanism involving RBCK1-mediated ubiquitination and degradation of IRF3.