O-乙酰氨基葡萄糖(O-GlcNAc)修饰及其生物学功能研究进展

O-GlcNAcylation and related research progress in biological function

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。

Abstract:

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.