Advances in Strategies and Tools Available for Interrogation of Protein O‐GlcNAcylation

The attachment of a single O-linked β-N-acetylglucosamine (O-GlcNAc) to serine and threonine residues of numerous proteins in the nucleus, cytoplasm, and mitochondria is a reversible post-translational modification (PTM) and plays an important role as a regulator of various cellular processes in both healthy and disease states. Advances in strategies and tools that allow for the detection of dynamic O-GlcNAcylation on cellular proteins have helped to enhance our initial and ongoing understanding of its dynamic effects on cellular stimuli and given insights into its link to the pathogenesis of several chronic diseases. Furthermore, chemical genetic strategies and related tools have been successfully applied to a myriad of biological systems with a new level of spatiotemporal and molecular precision. These strategies have started to be used in studying and controlling O-GlcNAcylation both in vivo and in vitro. In this minireview, overviews of recent advances in molecular tools being applied to the detection and identification of O-GlcNAcylation on cellular proteins as well as on individual proteins are provided. In addition, chemical genetic strategies that have already been applied or are potentially usable in O-GlcNAc functional are also discussed.