Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, U.S.A.
Biochem Soc Trans. 2021 Dec 17;49(6):2891-2901. doi: 10.1042/BST20210865.
O-linked N-acetylglucosamine (O-GlcNAc) is a widespread reversible modification on nucleocytoplasmic proteins that plays an important role in many biochemical processes and is highly relevant to numerous human diseases. The O-GlcNAc modification has diverse functional impacts on individual proteins and glycosites, and methods for editing this modification on substrates are essential to decipher these functions. Herein, we review recent progress in developing methods for O-GlcNAc regulation, with a focus on methods for editing O-GlcNAc with protein- and site-selectivity in cells. The applications, advantages, and limitations of currently available strategies for writing and erasing O-GlcNAc and future directions are also discussed. These emerging approaches to manipulate O-GlcNAc on a target protein in cells will greatly accelerate the development of functional studies and enable therapeutic interventions in the O-GlcNAc field.
O-连接 N-乙酰葡萄糖胺(O-GlcNAc)是一种广泛存在的、可逆的核细胞质蛋白修饰,在许多生化过程中发挥着重要作用,与许多人类疾病密切相关。O-GlcNAc 修饰对单个蛋白质和糖基化位点具有多种功能影响,并且对底物进行这种修饰的编辑方法对于破译这些功能至关重要。本文综述了近年来开发 O-GlcNAc 调控方法的进展,重点介绍了在细胞中具有蛋白质和位点选择性编辑 O-GlcNAc 的方法。还讨论了目前用于写入和擦除 O-GlcNAc 的策略的应用、优点和局限性,以及未来的发展方向。这些在细胞中针对靶蛋白操纵 O-GlcNAc 的新兴方法将极大地促进功能研究的发展,并能够在 O-GlcNAc 领域进行治疗干预。