RNF135 is a positive regulator of IFN expression and involved in RIG-I signaling pathway by targeting RIG-I
RNF135 is a positive regulator of IFN expression and involved in RIG-I signaling pathway by targeting RIG-I
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RNF135 是 IFN 表达的正调节因子，并通过靶向 RIG-I 参与 RIG-I 信号通路
DOI：
10.1016/j.fsi.2018.11.070
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发表时间：
2019-03-01
影响因子：
4.7
通讯作者：
Liu, Zhaoyu
中科院分区：
文献类型：
--
作者：
Lai, Yuxiong;Liang, Min;Liu, Zhaoyu
RIG-I样受体（RLR）在抗病毒和炎症反应中起关键作用。越来越多的证据表明，泛素化在RIG-I信号通路的调控中起着至关重要的作用。据报道，几种泛素连接酶参与RIG-I介导的信号转导。在本研究中，我们证明了斑马鱼RING指蛋白135（zbRNF 135）是RIG-I信号通路调控的关键球员。zbRNF 135 mRNA在斑马鱼不同组织中广泛表达。在体内和体外，poly（I：C）处理后zbRNF 135的表达上调。ZbRNF 135的过表达上调了ZF 4细胞中RIG-I信号通路相关基因（LGP 2、MDA 5、RIG-I、MAVS、TRAF 3、IRF 3和IRF 7）及其下游分子（IFN 1、ISG 15、Mx和PKR）的表达谱。荧光素酶和泛素化分析表明，zbRNF 135的过表达促进斑马鱼RIG-I（zbRIG-I）介导的IFN 1启动子激活介导的K63连接的zbRIG-I的泛素化。免疫共沉淀实验表明zbRNF 135与zbRIG-I特异性相互作用。我们的研究表明zbRNF 135通过调节RIG-I信号通路参与天然免疫应答。
RIG-I-like receptors (RLRs) play a key role in antiviral and inflammatory responses. Increasing evidence indicates that ubiquitination is crucial for regulation of RIG-I signaling pathway. Several ubiquitin ligases were reported to be involved in RIG-I-mediated signal transduction. In the present study, we demonstrated zebrafish RING finger protein 135 (zbRNF135) was a critical player in the regulation of RIG-I signaling pathway. zbRNF135 mRNA was widely expressed in different tissues of zebrafish. The expression of zbRNF135 was up regulated post poly(I:C) treatment in vivo and in vitro. Furthermore, the expression profiles of RIG-I signaling pathway related genes (LGP2, MDA5, RIG-I, MAVS, TRAF3, IRF3 and IRF7), together with its downstream molecules (IFN1, ISG15, Mx and PKR), were up-regulated by overexpression of zbRNF135 in ZF4 cells. Luciferase and ubiquitination assays revealed that overexpression of zbRNF135 facilitated zebrafish RIG-I (zbRIG-I)-mediated IFN1 promoter activation by mediating K63-linked ubiquitination of zbRIG-I. The co-immunoprecipitation assay showed that zbRNF135 specifically interacted with zbRIG-I. Our study indicated that zbRNF135 participated in innate immune response through modulating RIG-I signaling pathway.