Chemical Biology of Glycoproteins
CHAPTER 4: Chemical Biology of O-GlcNAc Glycosylation
Published:20 Mar 2017
O-Linked β-N-acetylglucosamine (O-GlcNAc) is a critical intracellular post-translational modification, decorating thousands of nuclear, cytoplasmic, and mitochondrial proteins. O-GlcNAc governs myriad aspects of cell physiology, including cell-cycle progression, cell metabolism, and cell death, and is essential, as genetic ablation of the O-GlcNAc-cycling enzymes is lethal in mice. Importantly, O-GlcNAc signaling is dysregulated in numerous human diseases, such as cancer, diabetes, and cardiac arrhythmia. Despite this broad pathophysiological significance, major aspects of O-GlcNAc signaling remain obscure. Moreover, because O-GlcNAc is a rapidly cycling post-translational modification, it can be challenging to study using traditional genetic or cell biological methods alone. In this context, chemical biology has offered a range of powerful tools to advance our understanding of O-GlcNAc in a wide variety of experimental systems. Here, we review the major contributions that chemical methods have made to the study of this vital signaling modification, and we highlight some important outstanding questions in O-GlcNAc biology that may be addressed by future chemical approaches.