(1 上海交通大学系统生物医学研究院系统生物医学教育部重点实验室,上海 200240;2 上海交通大学癌基因及相关基因国家重点实验室,上海 200240)

摘 要:摘 要:糖基化作为一种主要的蛋白翻译后修饰形式,在复杂的生命活动中扮演着重要角色。1984年由G.W. Hart等发现的O-GlcNAc糖基化因不同于传统的糖基化并具有重要的生物学功能,近年来引起极大的关注。O-GlcNAc糖基化的修饰机制类似于磷酸化,参与了基因转录、信号转导和细胞生长与分化等多个重要的生物学过程。此外相关研究发现,2型糖尿病、癌症及神经退行性疾病等的发生均与O-GlcNAc糖基化和磷酸化的异常相关,但是对于O-GlcNAc糖基化的功能研究目前还存在很多亟待解决的问题。就O-GlcNAc糖基化的背景、O-GlcNAc糖基化的功能研究最新进展及相关疾病的研究现状进行了简单总结,并对目前O-GlcNAc糖基化研究中所存在的重要问题进行探讨,同时,将近年来新兴的蛋白质芯片技术应用到O-GlcNAc糖基化机制及功能的研究中,或许能够为O-GlcNAc的研究提供一种新思路。
关键词:O-GlcNAc糖基化;O-GlcNAc transferase;O-GlcNAcase;蛋白质底物;蛋白质相互作用

Recent advancements in the functional study of protein O-GlcNAcylation
DENG Rui-Ping1,2, GUO Shu-Juan1,2, TAO Sheng-Ce1,2*
(1 Shanghai Center for Systems Biomedicine, Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Jiaotong University, Shanghai 200240, China; 2 State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiaotong University, Shanghai 200240, China)

Abstract: Abstract: As one of the most important protein post-translational modifications (PTMs), glycosylation plays critical roles in a variety of biological processes. Among all known formats of protein glycosylation, the O-GlcNAcylation, which was discovered by G.W. Hart in 1984, is very unique from  the ‘‘classical” glycosylations and also functionally very important. O-GlcNAcylation is similar to protein phosphorylation and involved in many cellular functions such as gene expression, signal transduction, cell differentiation and etc. Recent studies show that O-GlcNAcylation is highly related to many challenging diseases, e.g., diabetes, cancer and degenerative diseases that we are facing today. However, how O-GlcNAcylation is related to these diseases and what’s the underlying molecular mechanism is still elusive. Herein, we have discussed the basic background of O-GlcNAcylation, summarized the recent advancement in O-GlcNAcylation study and its roles in diseases. We have also addressed some of the challenges that we are facing in O-GlcNAcylation study. To tackle these challenges, protein microarray technology may be a good choice because of its high-throughput and parallel analysis capabitlity, e.g., protein microarray is suitable for global identification of regulators and substrates of O-GlcNAc transferase.
Key words: O-GlcNAcylation; O-GlcNAc transferase;  O-GlcNAcase; protein substrate; protein-protein interaction

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