糖基化与泛素化修饰在疾病发生发展及病毒感染中交互作用的研究进展

doi:10.13481/j.1671-587X.20260530

摘要/Abstract

摘要：

糖基化和泛素化是两类广泛存在的蛋白质翻译后修饰（PTM）方式，二者通过交互作用构成动态调控网络，共同参与调控蛋白质稳态、信号转导级联反应和细胞分化及发育等关键生物学过程。糖基化修饰可通过调控泛素连接酶活性及其底物特异性，影响泛素化进程；反之，泛素化修饰则可通过改变糖基转移酶稳定性和底物空间构象，反向调控糖基化修饰的发生和修饰类型。现有证据表明：上述2种修饰的动态平衡失调及其调控网络的紊乱与肿瘤发生发展、病毒免疫逃逸和代谢综合征等病理过程存在密切关联。本文结合近年来国内外相关研究进展，对糖基化与泛素化修饰的生物学功能和二者在肿瘤等疾病发生发展及病毒感染中的相互调控作用进行综述，探讨将糖基化与泛素化修饰涉及的关键分子作为潜在治疗靶点的可行性，以期为肿瘤和病毒感染的治疗策略提供理论支撑。

关键词: 糖基化, 泛素化, 去泛素化酶, 肿瘤, 病毒

Abstract:

Glycosylation and ubiquitination are two prevalent forms of post-translational modification（PTM） of proteins. They form a dynamic regulatory network through their interactions， jointly participating in the regulation of key biological processes such as maintenance of protein homeostasis， signal transduction cascades， and cellular differentiation and development. Glycosylation can influence the ubiquitination process by regulating the activity and substrate specificity of ubiquitin ligase. Conversely， ubiquitination can reciprocally regulate the occurrence and types of glycosylation by altering the stability of glycosyltransferases and the spatial conformation of their substrates. Current evidence indicates that the dysregulation of the dynamic balance of these two modifications and the disruption of their regulatory network are closely associated with pathological processes such as tumorigenesis and progression， viral immune evasion， and metabolic syndrome. Based on recent domestic and international literature， this article summarized the biological functions of glycosylation and ubiquitination modifications， as well as their mutual regulatory roles in the development and progression of diseases including tumor and viral infection. The feasibility of targeting key molecules involved in the glycosylation and ubiquitination processes as potential therapeutic targets was also discussed， aiming to provide theoretical support for the treatment strategies of tumor and viral infection.

Key words: Glycosylation, Ubiquitination, Deubiquitinating enzyme, Tumor, Virus

中图分类号:

高源,高文英,张文艳. 糖基化与泛素化修饰在疾病发生发展及病毒感染中交互作用的研究进展[J]. 吉林大学学报(医学版), 2026, 52(5): 1483-1490.

Yuan GAO,Wenying GAO,Wenyan ZHANG. Research progress in interaction of glycosylation and ubiquitination modifications in disease occurrence and development and viral infection[J]. Journal of Jilin University(Medicine Edition), 2026, 52(5): 1483-1490.

图/表 1

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Disease classification	Disease	Cellular component	Mechanism	Literature
Cancer	Breast cancer	PD-1	Incomplete glycosylation of PD-1 promotes its ubiquitination and degradation.	[35-37]
		MDM2	MDM2 directs PD-1 degradation by facilitating its deglycosylation and subsequent ubiquitination coupling.	[27]
		PD-L1 GSK-3β	Glycosylation of PD-L1 inhibits GSK-3β activity, thereby inhibiting GSK-3β- mediated ubiquitination and degradation of PD-L1.	[28]
		PD-L1 TMUB1	TMUB1 inhibits polyubiquitination of PD-L1 at the K281 site in the endoplasmic reticulum, and it enhances PD-L1 stability by recruiting STT3A to promote its N-glycosylation.	[29]
		B7-H4	N-glycosylation of B7-H4 antagonizes its ubiquitination and subsequent degradation mediated by the E3 ligase AMFR.	[30]
	OV	SUN2 FBXO2	FBXO2 is abnormally highly expressed, and it recognizes and targets glycosylated SUN2 for its ubiquitination degradation, thereby inhibiting apoptosis.	[31]
	Cervical cancer	MLL5 OGT USP7	The stability of MLL5 protein is synergistically regulated by OGT and USP7, and overexpression of OGT inhibits the ubiquitination of MLL5.	[32]
	Liver cancer	XIST miR-424-5p RAF1	Down-regulation of XIST and miR-424-5p reduces OGT expression, thereby inhibiting RAF1 glycosylation and promoting its ubiquitinated degradation.	[46]
Infection	HCV VSV SARS-CoV-2 HIV	FUT8 EGFR RIG-Ⅰ	The envelope proteins of these viruses induce the production of FUT8; FUT8 inhibits endogenous RIG-Ⅰ-mediated antiviral immune evasion by enhancing EGFR-mediated activation of N-core fucosylation, and also promotes ubiquitinated degradation of RIG-Ⅰ.	[48]
Cardiovascular disease	Atherosclerosis myocarditis	A20	O-GlcNAcylation of A20 is associated with ubiquitination and is involved in targeting it for ubiquitin-proteasome degradation.	[52]