Ⅰ型干扰素通路的泛素化调控

Regulation of typeⅠinterferon signaling by ubiquitination

天然免疫系统在机体快速识别、清除病原、维持自身稳定过程中发挥重要作用。其中Ⅰ型干扰素(type Ⅰ interferon,IFN-Ⅰ)通路是抗病毒天然免疫最重要的机制之一,其多种关键信号蛋白均受泛素化及类泛素化修饰调控,将免疫反应维持在适当的水平:一方面促进免疫反应抑制病毒感染;另一方面防止因免疫过度激活而产生炎症及自身免疫。本文对IFN-Ⅰ通路中关键信号蛋白的泛素化修饰以及类泛素化修饰的研究进展进行综述,对相关的E3泛素连接酶、去泛素化酶对天然免疫的修饰类型、修饰位点及其在抗病毒天然免疫中的作用进行了归纳总结。随着对IFN-Ⅰ通路的泛素化、类泛素化调控研究的进一步深入,新型靶向E3泛素连接酶、去泛素化酶的药物将在抗病毒、肿瘤、自身免疫疾病方面具有广阔的应用前景。

The innate immune system is critical for the initial detection and elimination of invading pathogens,contributing to the maintenance of body homeostasis.TypeⅠinterferon(IFN-Ⅰ)-mediated antiviral response,vital for host innate antiviral immunity,is extensively regulated by ubiquitination and ubiquitin-like modifications to maintain the innate antiviral response at an appropriate level:on one hand,the ubiquitination potentiates innate immunity to combat viral infections;on the other hand,ubiquitination also serves as a"brake mechanism"to avoid excessive activation of immunity and autoimmune diseases.This paper reviews the research progress of the ubiquitination and ubiquitin-like modifications of key signaling proteins in IFN-Ⅰsignaling.The modification types,sites and their roles in antiviral innate immunity were summarized.Further understanding of ubiquitination of IFN-Ⅰsignaling will help to develop new drugs targeting E3 ubiquitin ligase and deubiquitinase,which has broad application prospects in anti-virus,antitumor and autoimmune diseases.