UFMylation类泛素修饰在结核分枝杆菌感染免疫中的作用与机理

doi:10.16288/j.yczz.24-259

遗传 ›› 2025, Vol. 47 ›› Issue (5): 546-557.doi: 10.16288/j.yczz.24-259

UFMylation类泛素修饰在结核分枝杆菌感染免疫中的作用与机理

廖怡然¹(), 张其奥¹, 李佩波²(), 谢建平¹^,²()

1.西南大学生命科学学院现代生物医药研究所，重庆 400715
2.重庆市公共卫生救治中心，重庆 400036

收稿日期:2024-10-30 修回日期:2024-12-31 出版日期:2025-05-20 发布日期:2025-01-06
通讯作者: 谢建平，博士，研究员，研究方向：结核分枝杆菌等重要病原致病耐药机理与新防控措施研发。E-mail: georgex@swu.edu.cn；
李佩波，硕士，主任医师，研究方向：传染病诊治。E-mail: 157318851@qq.com
作者简介:廖怡然，硕士研究生，专业方向：微生物感染与免疫。E-mail: 1668704934@qq.com
基金资助:
国家自然科学基金项目(82211530059);2023年重庆市公共卫生重点专科(学科)建设项目(CSTB2024NSCQ-MSX0703);重庆市科卫联合医学科研项目(2023MSXM107)

The role and mechanism of UFMylation, a ubiquitin-like modification, in Mycobacterium tuberculosis infection immunity

Yiran Liao¹(), Qiao Zhang¹, Peibo Li²(), Jianping Xie¹^,²()

1. Institute of Modern Biopharmaceuticals, School of Life Sciences, Southwest University, Chongqing 400715, China
2. Chongqing Public Health Medical Center, Chongqing 400036, China

Received:2024-10-30 Revised:2024-12-31 Published:2025-05-20 Online:2025-01-06
Supported by:
National Natural Science Foundation of China(82211530059);2023 Key Disciplines On Public Health Construction in Chongqing(CSTB2024NSCQ-MSX0703);Chongqing medical scientific research project (Joint project of Chongqing Health Commission and Science and Technology Bureau)(2023MSXM107)

摘要/Abstract

摘要：

Ubiquitin-fold modifier 1 (UFM1)是一种在原核生物和大多数真核生物中广泛存在的I型类泛素蛋白，其介导的UFMylaiton修饰参与调节多种细胞生化过程。近年来UFM1系统在内质网稳态调节中的重要性被逐步发现和重视。结核分枝杆菌感染引发的内质网应激是结核病发病进程的重要环节，因而UFM1系统有望成为抗结核治疗药物研发的新靶标。本文对UFM1系统和其介导的UFMylation途径进行了介绍，并重点综述了UFM1系统参与内质网稳态调节的最新进展及其在结核病治疗中的潜在价值，以期为开发新型抗结核治疗方法提供新的方向。

关键词: UFMylation, UFM1系统, 结核病

Abstract:

Ubiquitin-fold modifier 1 (FM1) is a ubiquitin-like type I protein widely present in prokaryote and most eukaryote. UFMylaiton, mediated by UFM1, is involved in the regulation of a variety of cellular biochemical processes. Recently, the importance of UFM1 system in endoplasmic reticulum homeostasis regulation has been gradually discovered and emphasized. Endoplasmic reticulum stress caused by Mycobacterium tuberculosis is an important link in the progression of tuberculosis, so UFM1 system is expected to become a new target for the development of anti-tuberculosis drugs. In this review, we provide a brief overview of the UFM1 system and UFMylation pathway, and summarize the recent advances in understanding UFM1’s role in ER homeostasis regulation and its potential value in TB treatment, with the aim of offering new insight and direction for developing novel therapeutic strategies against tuberculosis.

Key words: UFMylation, UFM1 system, tuberculosis

廖怡然, 张其奥, 李佩波, 谢建平. UFMylation类泛素修饰在结核分枝杆菌感染免疫中的作用与机理[J]. 遗传, 2025, 47(5): 546-557.

Yiran Liao, Qiao Zhang, Peibo Li, Jianping Xie. The role and mechanism of UFMylation, a ubiquitin-like modification, in Mycobacterium tuberculosis infection immunity[J]. Hereditas(Beijing), 2025, 47(5): 546-557.

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信号通路	通路功能	CDK5RAP3扮演的角色	参考文献
Wnt/β-catenin 信号通路	在胚胎发育、组织再生和干细胞维持的多个阶段发挥重要作用，其异常激活与多种类型的癌症相关	通过磷酸化GSK-3β抑制β-catenin，从而抑制胃癌发生	[29]
		通过Akt/GSK-3β使Wnt/β-catenin通路失活，从而抑制类甲状腺癌的发生	[30]
		通过抑制胃癌细胞AKT磷酸化抑制Wnt/β-catenin信号传导，从而抑制胃癌发生	[31]
蛋白激酶ERK信号通路	参与调控细胞周期和细胞分化，细胞响应外界刺激的必需途径	作为抑瘤因子，在ERK1/2信号通路调控下抑制胃癌干细胞样细胞的自我更新	[32]
血管内皮生长因子(VEGF) 信号通路	在血管的形成和生长过程中起着重要作用。VEGF在新生血管形成过程中诱导基因表达，调控血管通透性并促进细胞的迁移、增殖和存活	抑制AKT/HIF-1α/VEGFA信号传导，从而抑制胃神经内分泌癌血管生成	[33]
信号转导与转录激活因子3(STAT3)信号通路	调节细胞周期蛋白和抗凋亡因子，促进细胞增殖和存活	通过与TSPAN6相互作用调控STAT3信号通路，影响胶质母细胞瘤的恶性发展	[34]

类别	泛素/类泛素蛋白	靶向/编码蛋白病原体	蛋白功能	生理学效应	参考文献
宿主编码	USP18	淋巴细胞脉络丛脑膜炎病毒	去ISG化	调节干扰素信号传导	[56]
	USP18	水疱性口炎病毒	去ISG化	调节干扰素信号传导	[56]
	USP7	I型单纯疱疹病毒	去泛素化	稳定ICP0蛋白	[57]
	USP7	EB病毒	去泛素化	稳定EBNA1蛋白；调控其复制功能	[58]
	CYLD	不可分型流感嗜血杆菌	去泛素化	负调控NF-kB依赖性炎症	[59]
		肺炎链球菌		急性肺损伤，死亡率增加	[60]
		大肠杆菌		负调控NF-kB依赖性炎症	[61]
病原体编码	AvrA	沙门氏菌属	去泛素化	抑制宿主炎症反应	[62]
	SseL	沙门氏菌属	去泛素化	延缓巨噬细胞杀伤	[63]
	YopJ	耶尔森氏菌属	乙酰化、去泛素化、去SUMO化	抑制宿主炎症反应	[64]
	ChlaDub1 ChlaDub2	沙眼衣原体	去泛素化、去NEDD化	未知	[65]
	ElaD	大肠杆菌	去泛素化	未知	[66]

UFMylation类泛素修饰在结核分枝杆菌感染免疫中的作用与机理

The role and mechanism of UFMylation, a ubiquitin-like modification, in Mycobacterium tuberculosis infection immunity

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[1]	张其奥, 王子路, 李佩波, 谢建平. USP18介导的蛋白质去ISG化及其在结核病等传染病中的作用[J]. 遗传, 2023, 45(11): 998-1006.
[2]	刘洋, 王邦兴, 刘志永, 韩轶, 谭耀驹, 李昕洁, 刘健雄, 谭守勇, 张天宇. 非一线抗结核药物耐药机制及耐药性诊断研究进展[J]. 遗传, 2016, 38(10): 928-939.