O-乙酰氨基葡萄糖(O-GlcNAc)修饰及其生物学功能研究进展

摘要

O-GlcNAc修饰系发生在蛋白质丝氨酸、苏氨酸羟基末端连接的乙酰氨基葡萄糖上的单糖基修饰.自1984年以来,针对O-GlcNAc糖基化修饰的研究日益升温.O-GlcNAc修饰是动态变化、可调控的,满足蛋白质翻译后修饰参与信号通路的必要条件.在多数情况下,O-GlcNAc修饰与磷酸化修饰发生在蛋白质的相同氨基酸残基上,故两种修饰之间常存在竞争性抑制,亦被称之为“阴阳”制衡.O-GlcNAc修饰参与细胞内多种信号通路的调控,调节着生长、增殖、激素响应等过程,在糖尿病、神经退行性疾病和肿瘤等代谢性疾病中扮演重要角色.探究O-GlcNAc修饰及其在生理、病理状态中的作用具有极为重要的意义.%The O-linked N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation) is a post-translational modification that transfers N-acetylglucosamine to serine and/or threonine residues of target proteins.O-GlcNAcylation has been the research hotspot since it was first reported by Gerald Hart in the early 1980s.O-GlcNAcylation is so dynamical,inducible and active that it satisfies the prerequisites of the role of protein post-translational modification in signal transductions.In most cases,a competitive inhibition occurs between O-GlcNAcylation and phosphorylation due to their same modification sites in proteins,which is also called "Yin-yang" balance.O-GlcNAcylation has been proved to be associated with multiple cellular signaling pathways,including the regulation of growth,the effect on proliferation,and the response to hormone.Also,O-GlcNAcylation plays a key role in the development of metabolic diseases such as diabetes,neurodegenerative diseases and cancers.Based on the above,it is of great significance to explicate the bio-function of O-GlcNAcylation in physiological and pathological processes.