O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress.
O-linked beta-N-acetylglucosamine (O-GlcNAc): Extensive crosstalk with phosphorylation to regulate signaling and transcription in response to nutrients and stress.
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DOI：
10.1016/j.bbagen.2009.07.018
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发表时间：
2010-02
影响因子：
3
通讯作者：
Hart, Gerald W.
中科院分区：
文献类型：
--
作者：
Butkinaree, Chutikarn;Park, Kyoungsook;Hart, Gerald W.
关键词：
自20世纪80年代初发现以来，O-连接-β-N-乙酰葡萄糖胺（O-GlcNAc），丝氨酸或苏氨酸残基羟基上的单糖修饰，改变了我们对蛋白质糖基化的看法。虽然其他形式的蛋白质糖基化修饰细胞表面上或分泌机制的腔室内的蛋白质，O-GlcNAc修饰无数的核质蛋白。GlcNAc酰化蛋白参与转录、泛素化、细胞周期和应激反应。GlcNAc酰化在化学计量、定位和循环方面与蛋白质磷酸化相似。迄今为止，已知只有两种酶调节哺乳动物中的GlcNAc化：O-GlcNAc转移酶（OGT），其催化O-GlcNAc的添加;和β-N-乙酰氨基葡糖苷酶（O-GlcNAc酶），其是一种中性氨基己糖苷酶，负责O-GlcNAc的去除。OGT和O-GlcNAcase受RNA剪接、营养素和翻译后修饰的调节。它们的特异性由许多瞬时相关的靶向亚基控制。随着用于检测O-GlcNAc的方法的改进，我们对O-GlcNAc的功能的理解迅速增长。本文就GlcNAcylation在调节细胞过程中的作用、GlcNAcylation与蛋白质磷酸化的相互作用以及OGT和O-GlcNAcase的调节进行综述。GlcNAc酰化在其丰度、蛋白质分布及其在蛋白质上的循环和关闭方面与磷酸化竞争。GlcNAc酰化与磷酸化具有广泛的串扰，以调节信号传导、转录和响应营养和应激的细胞骨架。GlcNAc酰化和磷酸化之间的异常串扰是糖尿病中失调的基础，包括葡萄糖毒性，并且缺陷性GlcNAc酰化涉及神经变性疾病和癌症，并且最近涉及AIDS。
Since its discovery in the early 1980s, O-linked-β-N-acetylglucosamine (O-GlcNAc), a single sugar modification on the hydroxyl group of serine or threonine residues, has changed our views of protein glycosylation. While other forms of protein glycosylation modify proteins on the cell surface or within luminal compartments of the secretory machinery, O-GlcNAc modifies myriad nucleocytoplasmic proteins. GlcNAcylated proteins are involved in transcription, ubiquitination, cell cycle, and stress responses. GlcNAcylation is similar to protein phosphorylation in terms of stoichiometry, localization and cycling. To date, only two enzymes are known to regulate GlcNAcylation in mammals: O-GlcNAc transferase (OGT), which catalyzes the addition of O-GlcNAc, and β-N-acetylglucosaminidase (O-GlcNAcase), a neutral hexosaminidase responsible for O-GlcNAc removal. OGT and O-GlcNAcase are regulated by RNA splicing, by nutrients, and by post-translational modifications. Their specificities are controlled by many transiently associated targeting subunits. As methods for detecting O-GlcNAc have improved our understanding of O-GlcNAc's functions has grown rapidly. In this review, the functions of GlcNAcylation in regulating cellular processes, its extensive crosstalk with protein phosphorylation, and regulation of OGT and O-GlcNAcase will be explored. GlcNAcylation rivals phosphorylation in terms of its abundance, protein distribution and its cycling on and off of proteins. GlcNAcylation has extensive crosstalk with phosphorylation to regulate signaling, transcription and the cytoskeleton in response to nutrients and stress. Abnormal crosstalk between GlcNAcylation and phosphorylation underlies dysregulation in diabetes, including glucose toxicity, and defective GlcNAcylation is involved in neurodegenerative disease and cancer and most recently in AIDS.
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