The E3 Ubiquitin Ligase RNF5 Targets Virus-Induced Signaling Adaptor for Ubiquitination and Degradation
The E3 Ubiquitin Ligase RNF5 Targets Virus-Induced Signaling Adaptor for Ubiquitination and Degradation
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E3 泛素连接酶 RNF5 针对病毒诱导的信号转导接头进行泛素化和降解
DOI：
10.4049/jimmunol.0903748
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发表时间：
2010-06-01
影响因子：
4.4
通讯作者：
Shu, Hong-Bing
中科院分区：
文献类型：
--
作者：
Zhong, Bo;Zhang, Yu;Shu, Hong-Bing
病毒感染可激活转录因子，如核因子-kappaB和干扰素调节因子3，这些转录因子协同诱生I型干扰素，并引发先天抗病毒反应。病毒诱导的信号转接子(VISA)已被确定为病毒触发的I型IFN诱导所需的关键转接子。在本研究中，我们发现E3泛素连接酶RNF5(RNF5)与VISA在线粒体上以病毒感染依赖的方式相互作用。结构域映射实验表明，VISA的C末端跨膜区是其与RNF5相互作用所必需的。RNF5靶向于K362和K461的VISA，以实现病毒感染后K48相关的泛素化和降解，而RNF5的敲除在早期逆转了病毒诱导的VISA下调。这些发现表明，RNF5介导的泛素化和VISA的降解是病毒触发的I型IFN诱导和细胞抗病毒反应的调节机制之一。免疫学杂志，2010,184：6249-6255。
Viral infection activates transcription factors, such as NF-kappa B and IFN regulatory factor 3, which collaborate to induce type I IFNs and elicit innate antiviral response. Virus-induced signaling adaptor (VISA) has been identified as a critical adaptor required for virus-triggered induction of type I IFNs. In this study, we showed that the E3 ubiquitin ligase RING-finger protein 5 (RNF5) interacted with VISA at mitochondria in a viral infection-dependent manner. Domain mapping experiments indicated that the C-terminal transmembrane domain of VISA was required for its interaction with RNF5. RNF5 targeted VISA at K362 and K461 for K48-linked ubiquitination and degradation after viral infection, whereas knockdown of RNF5 reversed virus-induced down-regulation of VISA at the early phase. These findings suggest that RNF5-mediated ubiquitination and degradation of VISA is one of the mechanisms of the regulation of virus-triggered induction of type I IFNs and cellular antiviral response. The Journal of Immunology, 2010, 184: 6249-6255.