O-GlcNAc glycosylation: From reductionism to systems biology

The dynamic posttranslational modification of proteins by O-linked-β-N-acetylglucosamine (O-GlcNAc glycosylation) plays many important roles in physiol. and disease. Remarkably, only a single enzyme catalyzes the modification, raising the question of how this enzyme (O-GlcNAc transferase or OGT) selects from among its diverse substrates to regulate specific cellular processes. Here we will describe a new systems-level approach for studying the functions, specificity, and regulation of O-GlcNAc glycosylation. Elucidation of these dynamic O-glycosylation networks provides insights into the key functions of this modification and may reveal novel approaches for therapeutic intervention.