Deciphering the Functions of Protein O-GlcNAcylation with Chemistry

详细信息    查看全文

• 作者：Matthew Worth ; Hao Li ; Jiaoyang Jiang
• 刊名：ACS Chemical Biology
• 出版年：2017
• 出版时间：February 17, 2017
• 年：2017
• 卷：12
• 期：2
• 页码：326-335
• 全文大小：589K
• ISSN：1554-8937

文摘

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.