泛素化修饰在RLR信号通路中的研究进展

病毒入侵后被细胞的模式识别受体RIG-I样受体（RIG-I-like receptor, RLR）识别从而启动抗病毒RLR信号通路的激活，先天免疫反应的异常激活将导致慢性炎症和免疫器官损伤，甚至引起自身免疫性疾病。为了防止抗病毒信号过早激活或过度激活，机体建立了完善的调节系统防止信号传导过程发生紊乱。蛋白的翻译后修饰（Post-translational modification, PTM）是调节模式识别受体及其下游信号蛋白稳定性和活性的关键机制，而泛素化（Ubiquitination, UB）作为蛋白质翻译后修饰的重要部分在抗病毒信号通路中被广泛研究。其中K48和K63连接的泛素化最为常见，通过K48连接的泛素链能够引起靶蛋白通过蛋白酶体途径降解，而K63连接的泛素链能够促进蛋白激活和细胞信号转导。RIG-Ⅰ、MAVS、TBK1以及TRAF家族相关蛋白作为RLR通路的信号传递分子，其蛋白的泛素化修饰也成为研究的重点。本文讨论了K48和K63泛素化在抗病毒免疫信号通路中的研究进展，特别是RIG-I样受体引发的信号传导途径中蛋白的泛素化修饰。

Research progress of ubiquitination mechanism in RLR signaling pathway

Invading virus is recognized by one of pattern recognition receptors, RIG-I-like receptor (RLR), to activate antiviral RLR signaling pathway. Abnormal activation of PRRs will lead to chronic inflammation, immune organ damage, and even autoimmune diseases. In order to prevent the premature or excessive activation of antiviral signals, the body has established a perfect regulatory system to prevent the disorder of signal transduction process. Post-translational modification (PTM) of proteins is a key mechanism for regulating the stability and activity of pattern recognition receptors and their downstream signaling proteins, while ubiquitination (UB) is an important part of protein post-translational modification in antiviral signaling pathways have been extensively studied. Of these, K48- and K63-linked ubiquitination is the most common: K48-linked ubiquitin chains can cause degradation of target proteins via the proteasomal pathway, while K63-linked ubiquitin chains can promote protein activation and cell signaling. RIG-I, MAVS, TBK1 and TRAF family member proteins are the signaling molecules of RLR signaling, and the ubiquitination mechanism of these proteins has also been studied. Here, we discuss the research progress of K48 and K63 ubiquitination in antiviral immune signaling pathways, especially the ubiquitination modification of proteins in signaling pathways triggered by RIG-I-like receptors.