AUTHOR=Saha Abhijit , Fernández-Tejada Alberto 

TITLE=Chemical biology tools to interrogate the roles of O-GlcNAc in immunity

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1089824

DOI=10.3389/fimmu.2022.1089824

ISSN=1664-3224

ABSTRACT=<p>The <italic>O</italic>-linked β-<italic>N</italic>-acetylglucosamine (<italic>O</italic>-GlcNAc) glycosylation of proteins is an essential and dynamic post-translational modification in mammalian cells that is regulated by the action of two enzymes. <italic>O</italic>-GlcNAc transferase (OGT) incorporates this monosaccharide on serine/threonine residues, whereas <italic>O</italic>-GlcNAcase (OGA) removes it. This modification is found on thousands of intracellular proteins involved in vital cellular processes, both under physiological and pathological conditions. Aberrant expression of <italic>O</italic>-GlcNAc has been implicated in diseases such as Alzheimer, diabetes, and cancer, and growing evidence over the last decade has also revealed key implications of <italic>O</italic>-GlcNAcylation in immunity. While some key signaling pathways involving <italic>O</italic>-GlcNAcylation in immune cells have been discovered, a complete mechanistic understanding of how <italic>O</italic>-GlcNAcylated proteins function in the immune system remains elusive, partly because of the difficulties in mapping and quantifying <italic>O</italic>-GlcNAc sites. In this minireview, we discuss recent progress on chemical biology tools and approaches to investigate the role of <italic>O</italic>-GlcNAcylation in immune cells, with the intention of encouraging further research and developments in chemical glycoimmunology that can advance our understanding of <italic>O</italic>-GlcNAc in immunity.</p>