Deciphering the Functions of Protein O-GlcNAcylation with Chemistry.
Deciphering the Functions of Protein O-GlcNAcylation with Chemistry.
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DOI：
10.1021/acschembio.6b01065
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发表时间：
2017-02-17
影响因子：
4
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Worth M;Li H;Jiang J
O-GlcNAc化是细胞内蛋白质上的丝氨酸和苏氨酸残基被β-N-乙酰葡糖胺（O-GlcNAc）修饰。这种动态修饰通过O-GlcNAc转移酶（OGT）连接并通过O-GlcNAc酶（OGA）去除，并且是各种细胞过程的关键调节剂。此外，O-GlcNAc酰化在许多疾病中失调，例如糖尿病、癌症和阿尔茨海默病。然而，这种修饰及其循环酶（OGT和OGA）在正常和疾病状态中的确切作用仍然难以捉摸。这部分是由于用传统的遗传和生物化学技术研究O-GlcNAc化的困难。在本文中，我们将总结化学方法克服这些障碍的最新进展。我们将涵盖OGT和OGA的新抑制剂，代谢标记和细胞成像的进展，获得同质O-GlcNAc酰化蛋白质的合成方法，以及识别O-GlcNAc-蛋白质相互作用的交联方法。我们还将讨论我们的工具箱中剩余的差距，用于研究O-GlcNAcylation和尚未回答的高度感兴趣的问题。
O-GlcNAcylation is the modification of serine and threonine residues with β-N-acetylglucosamine (O-GlcNAc) on intracellular proteins. This dynamic modification is attached by O-GlcNAc transferase (OGT) and removed by O-GlcNAcase (OGA) and is a critical regulator of various cellular processes. Furthermore, O-GlcNAcylation is dysregulated in many diseases, such as diabetes, cancer, and Alzheimer’s disease. However, the precise role of this modification and its cycling enzymes (OGT and OGA) in normal and disease states remains elusive. This is partially due to the difficulty in studying O-GlcNAcylation with traditional genetic and biochemical techniques. In this review, we will summarize recent progress in chemical approaches to overcome these obstacles. We will cover new inhibitors of OGT and OGA, advances in metabolic labeling and cellular imaging, synthetic approaches to access homogeneous O-GlcNAcylated proteins, and cross-linking methods to identify O-GlcNAc-protein interactions. We will also discuss remaining gaps in our toolbox for studying O-GlcNAcylation and questions of high interest that are yet to be answered.
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影响因子：
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作者：
Griffin ME;Jensen EH;Mason DE;Jenkins CL;Stone SE;Peters EC;Hsieh-Wilson LC
通讯作者：
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影响因子：
7.4
作者：
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通讯作者：
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DOI：
10.1083/jcb.201501101
发表时间：
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期刊：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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