摘要
O-linked N-acetylglucosamine(O-GlcNAc)is a dynamic post-translational modification occurring on myriad proteins in the cell nucleus,cytoplasm,and mitochondria.The donor sugar for O-Glc NAcylation,uridine-diphosphate N-acetylglucosamine(UDP-Glc NAc),is synthesized from glucose through the hexosamine biosynthetic pathway(HBP).The recycling of O-GlcNAc on proteins is mediated by two enzymes in cells—O-GlcNAc transferase(OGT)and O-Glc NAcase(OGA),which catalyze the addition and removal of O-GlcNAc,respectively.O-GlcNAcylation is involved in a number of important cell processes including transcription,translation,metabolism,signal transduction,and apoptosis.Deregulation of O-GlcNAcylation has been reported to be associated with various human diseases such as cancer,diabetes,neurodegenerative diseases,and cardiovascular diseases.A better understanding of the roles of O-GlcNAcylation in physiopathological processes would help to uncover novel avenues for therapeutic intervention.The aim of this review is to discuss the recent updates on the mechanisms and impacts of O-GlcNAcylation on these diseases,and its potential as a new clinical target.
O-连接的N-乙酰葡萄糖胺(O-GlcNAc)修饰是一种发生于蛋白质丝氨酸或苏氨酸残基上的蛋白翻译后修饰,它能动态地发生在细胞的任何部位,如细胞质、线粒体、细胞核等。O-GlcNAc修饰的供体尿苷二磷酸-N-乙酰葡萄糖胺(UDP-GlcNAc)是己糖胺生物合成途径(HBP)的终产物。GlcNAc在蛋白上的添加和移除分别需要O-GlcNAc转移酶(OGT)和O-GlcNAc水解酶(OGA)的介导。被O-GlcNAc修饰的蛋白包括转录因子、代谢酶、细胞信号传导因子等。O-GlcNAc通过调控这些蛋白的功能参与到许多重要的生物进程中,如转录、翻译、代谢、信号传导、自噬等。此外,O-GlcNAc修饰的失调还与许多重要疾病息息相关,包括癌症、糖尿病、神经退行性疾病和心血管疾病。更好地了解O-GlcNAc修饰在这些疾病生理病理学进程中所起的作用将有助于开发新的治疗策略。本文介绍了O-GlcNAc与疾病病理联系的最新研究,并揭示O-GlcNAc可作为潜在的临床治疗靶点。
作者
Hao NIE
Wen YI
Hao NIE;Wen YI(MOE Laboratory of Biosystems Homeostasis&Protection,College of Life Sciences,Zhejiang University)
基金
supported by the National Natural Science Foundation of China(Nos.91753125,31270865,31322019,and 31570804)
the National Key Research and Development Program of China(No.2016YFA0100303)
the Zhejiang Provincial Natural Science Foundation of China(No.LR15C050001)
