USP18 介导的蛋白去泛素化及其在结核病和其他传染病中的作用。

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

机构信息

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.

出版信息

Yi Chuan. 2023 Nov 20;45(11):998-1006. doi: 10.16288/j.yczz.23-185.

DOI:10.16288/j.yczz.23-185

PMID:38764265

Abstract

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.

摘要

干扰素刺激基因 15（ISG15）的转录是由 I 型干扰素诱导的。ISG15 可以通过酶 E1、E2 和 E3 的顺序作用将靶蛋白共价修饰，这一过程称为 ISG 化。宿主蛋白的 ISG 化广泛参与免疫反应，如宿主抗病毒防御。泛素特异性蛋白酶 18（USP18）作为一种去泛素酶（DUB），可以通过抑制 I 型干扰素信号来去除靶蛋白上连接的 ISG15，并抑制宿主免疫反应。ISG15 或 USP18 介导的 ISGylation 和 deISGylation 的动态平衡在结核病中起着重要作用。此外，与 ISG15 类似，USP18 广泛参与病毒-宿主相互作用。在这篇综述中，我们总结了 ISG15 和 USP18 分别介导的 ISGylation 和 deISGylation 在结核病和其他重要疾病中的作用，以及潜在的调控网络。在这方面的进一步研究将激发新的以宿主为靶点的策略，以控制结核病等重要疾病。