USP18介导的蛋白质去ISG化及其在结核病等传染病中的作用  

USP18-mediated protein deISGylation and its role in tuberculosis and other infectious diseases

作　　者：张其奥 王子路 李佩波 谢建平[1,2] Qi’ao Zhang;Zilu Wang;Peibo Li;Jianping Xie(Institute of Modern Biopharmaceuticals,State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area,Key Laboratory of Eco-environments in Three Gorges Reservoir Region,Ministry of Education,School of Life Sciences,Southwest University,Chongqing 400715,China;Chongqing Public Health Medical Center,Chongqing 400036,China)

机构地区：[1]西南大学生命科学学院现代生物医药研究所,重庆400715 [2]重庆市公共卫生医疗救治中心,重庆400036

出　　处：《遗传》2023年第11期998-1006,共9页Hereditas（Beijing)

基　　金：国家自然科学基金项目(编号:82211530059,82072246)资助。

摘　　要：干扰素诱导基因15(interferon-stimulated gene 15,isg15)的表达受Ⅰ型干扰素诱导,该基因编码的蛋白ISG15可以分别通过E1、E2和E3酶的作用共价修饰靶蛋白,此过程被称为ISG化(ISGylation)。宿主蛋白的ISG化广泛参与天然免疫例如宿主的抗病毒过程。泛素特异性蛋白酶18(ubiquitin-specific protease 18,USP18)作为一种去泛素化酶(deubiquitinase,DUB)可以去除靶蛋白偶联的ISG15,并通过抑制Ⅰ型干扰素信号通路来抑制宿主的免疫应答。ISG15介导的ISG化和USP18介导的去ISG化(deISGylation)建立的动态平衡对结核病的发生、发展和转归有重要影响。此外,同ISG15一样,USP18也广泛参与病毒感染和宿主细胞抗病毒反应,多种先天性免疫疾病和免疫信号通路都受到USP18的调节。本文综述了ISG15和USP18相关的研究进展,重点介绍了ISG15介导的ISGylation和USP18介导的去ISG化在结核病及其他重要疾病中的调控作用,以期为靶向宿主蛋白的结核病等重要疾病防治提供新的策略。The transcription of interferon-stimulated gene 15(isg15)is induced by type I interferons.ISG15 can covalently modify target proteins through the sequential action of enzymesE1,E2,and E3,a process known as ISGylation.The ISGylation of host proteins is widely involved in immune responses,such as host antiviral defence.Ubiquitin-specific protease 18(USP18),as a deubiquitinase(DUB),can remove ISG15 conjugated to target proteins and inhibit host immune responses by suppressing the type I interferon signaling.The dynamic balance between ISGylation and deISGylation mediated by ISG15 or USP18 respectively plays a significant role in the tuberculosis.Furthermore,similar to ISG15,USP18 is extensively involved in virus-host interaction.In this review,we summarize the roles of ISGylation and deISGylation in tuberculosis and other important diseases mediated by ISG15 and USP18 respectively,underlying regulator network.Further studies in this aspect will inspire new host-targeted strategies to control important diseases such as tuberculosis.

关 键 词：USP18 ISG15 结核病 干扰素 

分 类 号：R51[医药卫生—内科学]