SOX9 negatively regulates the RLR antiviral signaling by targeting MAVS
SOX9 negatively regulates the RLR antiviral signaling by targeting MAVS
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DOI：
10.1007/s11262-022-01886-9
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发表时间：
2022-02-01
期刊：
影响因子：
1.6
通讯作者：
Xu，Liang-Guo
中科院分区：
文献类型：
--
作者：
Jiang，Xue;Xu，Liang-Guo
线粒体病毒诱导信号适配器 (MAVS)，也称为 VISA、IPS-1 和 Cardif，是 RIG-I 样受体 (RLR) 信号通路中的关键适配器蛋白。病毒感染后，RIG-I 识别病毒 dsRNA 并将其进一步转移到线粒体，在线粒体中通过其 CARD 结构域与 MAVS 结合，产生一系列信号级联。通过该信号级联的转导导致干扰素调节因子 3/7 (IRF3/IRF7) 的磷酸化和核转位以及 NF-κB 的激活，最终产生 I 型干扰素 (IFN) 和促炎细胞因子。在这里，我们的实验证明，SRY 相关的高迁移率组蛋白 9 (SOX9) 的过表达显着抑制仙台病毒 (SeV) 诱导和 MAVS 介导的 IFN-β 启动子和 ISRE 的激活。然而，敲除细胞中 SOX9 的表达会促进 SeV 诱导的 IFN-β 启动子和 ISRE 激活。进一步的研究表明，SOX9与MAVS相互作用，并靶向MAVS抑制MAVS-TRAF2的结合，从而抑制MAVS介导的TRAF2泛素化。综上所述，这些结果表明 SOX9 通过靶向 MAVS 下调 IFN-β 表达和抗病毒信号转导。
Mitochondrial virus-induced signal adaptor (MAVS), also known as VISA, IPS-1, and Cardif, is a crucial adaptor protein in the RIG-I-like receptor (RLR) signaling pathway. Upon viral infection, RIG-I recognizes viral dsRNA and further transfers it to mitochondria, where it binds to MAVS through its CARD domain, generating a series of signal cascades. Transduction through this signaling cascade leads to phosphorylation and nuclear translocation of interferon regulatory factor 3/7 (IRF3/IRF7) and activation of NF-κB, which ultimately produces type I interferon (IFN) and proinflammatory cytokines. Here, our experiments demonstrated that overexpression of SRY-related high-mobility group protein 9 (SOX9) significantly inhibited Sendai virus (SeV)-induced and MAVS-mediated activation of the IFN-β promoter and ISRE. However, knocking out the expression of SOX9 in cells promoted SeV-induced IFN-β promoter and ISRE activation. Further studies have shown that SOX9 interacts with MAVS and targets MAVS to inhibit the association of MAVS-TRAF2, thereby inhibiting MAVS-mediated TRAF2 ubiquitination. Taken together, these results indicate that SOX9 downregulates IFN-β expression and antiviral signal transduction by targeting MAVS.