泛素化修饰对维甲酸诱导基因I样受体家族(RLRs)信号通路分子调控作用的研究进展

Advances in the regulatory effects of ubiquitination on RLRs signaling pathways

摘要:

维甲酸诱导基因I样受体家族(retinoid acid-inducible gene-I-like receptors, RLRs)信号通路作为众多抗感染免疫信号通路之一，在诱导促炎细胞因子、趋化因子和I型干扰素产生等方面发挥重要的调控作用。作为蛋白质翻译后修饰之一的泛素化(ubiquitination)，是由泛素蛋白(ubiquitin)与目标蛋白上不同的氨基酸位点产生结合来调控蛋白的命运，如启动蛋白酶体途径降解蛋白或激活转运等功能。而RLRs信号通路分子的泛素化修饰既是调控多种效应因子的方式之一，也是病毒经此诱发动物重要疾病以及自身免疫病、慢性炎症的经典路径之一。本文主要综述RLRs信号通路中重要的效应器分子的典型结构特征、泛素化修饰类型和功能，探讨泛素化修饰调控RLRs信号通路关键分子的作用，为相关疾病的干预或治疗提供参考。

关键词:维甲酸诱导基因I样受体家族;泛素化;维甲酸诱导基因I;黑色素瘤分化相关蛋白5;遗传学与生理学实验室蛋白2

Abstract:

Retinoid acid-inducible gene-I-like receptor (RLR) signaling pathways, the immune signaling pathways in response to infections, play a regulatory role in the production of pro-inflammatory cytokines, chemokines, and type I interferons. Ubiquitination as one of the post-translational modifications refers to the process of ubiquitin binding to different amino acid sites on the target proteins, which regulates the fates of proteins. For example, it initiates the proteasome pathway to degrade the target protein or activating the protein transport. The ubiquitination of RLR signaling pathways is a way of regulating multiple effectors and one of the classical pathways through which viruses induce major diseases in animals, autoimmune diseases, and chronic inflammation. This paper introduces the typical structural features and the ubiquitination types of key effectors in the RLR signaling pathways. Furthermore, it expounds the roles of ubiquitination in the regulation of key molecules in the RLR signaling pathways, aiming to provide a reference for the intervention or treatment of related diseases.

Key words:retinoid acid-inducible gene-I-like receptors (RLRs);ubiquitination;retinoic-acid-inducible gene I (RIG-I);melanoma differentiation-associated antigen 5 (MDA5);laboratory of genetics and physiology 2 (LGP2)