葡糖酰胺(O-GlcNAc)修饰:细胞内糖基化的前世今生  

Intracellular O-GlcNAcylation: the One and the Only

作　　者：李静[1] 谭忠平 LI-Jing;TAN Zhong-Ping(Beijing Key Laboratory of DNA Damage Response,College of Life Sciences,Capital Normal University,Beijing 100048,China;Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China)

机构地区：[1]北京市DNA损伤应答重点实验室,首都师范大学生命科学学院,北京100048 [2]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《中国生物化学与分子生物学报》2020年第9期987-1001,共15页Chinese Journal of Biochemistry and Molecular Biology

基　　金：国家自然科学基金项目(No.31872720,91853120);新药创制国家科技重大专项(No.2018ZX09711001-013);国家重点研发计划政府间国际科技创新合作(No.2018YFE0111400);中国医学科学院北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室经费支持。

摘　　要：糖基化是一种古老的蛋白质翻译后修饰,常见于细胞外的糖被结构和细胞内部的内质网和高尔基体内。近年来,一种细胞内的糖基化修饰逐渐被大家所认识,这就是氧连接的N-乙酰葡糖胺(O-linkedβ-N-acetylglucosamine,O-GlcNAc)。它是唯一发生在细胞内的参与信号转导的糖修饰,一般发生于细胞质和细胞核中。自从20世纪80年代发现O-GlcNAc以来,生物学家和化学家一直在研究它修饰的位点和行使的生物学功能。O-GlcNAc修饰发生在丝氨酸和苏氨酸上,因此可以与磷酸化之间形成阴阳关系并参与信号转导过程。但由于其低丰度易水解的特点导致难以鉴定位点,又使研究人员难以见其真容。本文将回顾O-GlcNAc修饰的发现历史,介绍近年来发展的化学生物学手段对其位点的鉴定,并着重阐释该修饰在细胞周期以及表观遗传等生物过程中的功能。随着学科交叉及质谱技术的发展,古老而弥新的糖基化修饰将绽放出新的花蕾。Glycosylation,one of the ancient post-translational modifications,is often associated with extracellular glycocalyx or intracellular endoplasmic reticulum or the Golgi apparatus.Recently,an emerging intracellular glycosylation has caught our attention:O-linkedβ-N-acetylglucosamine(O-GlcNAc).As the only form of glycosylation that occurs in the cytosol and nucleus,O-GlcNAc was discovered in the 1980 s and has captured the interests of biologists and chemists alike.Mechanistically,it modifies the Ser and Thr residues of proteins,so it forms a yin-yang relationship with phosphorylation.Although vital for the signal transduction process,its innate low stoichiometry and high lability has impeded in-depth analysis of its modification site and function.In this review,we will provide a historical perspective on O-GlcNAc,and summarize how the recent development of chemical biology tools has sparked the glycosylation field,with a particular emphasis on its function in cell cycle control and epigenetics.As we take on a more inter-disciplinary approach with more advanced mass spectrometry technologies,we are bound to embrace a sweet future where O-GlcNAc studies will bloom and blossom.

关 键 词：氧连接的N-乙酰葡糖胺 糖基化 化学生物学 细胞周期 表观遗传 

分 类 号：O629.1[理学—有机化学] Q532[理学—化学]