The role of intracellular protein O-glycosylation in cell adhesion and disease☆

Post-translational protein modification, including phosphorylation, is generally quick and reversible, facilitating rapid biologic adjustments to altered cellular physiologic demands. In addition to protein phosphorylation, other post-translational modifications have been identified. Intracellular protein O-glycosylation, the addition of the simple sugar O-linked N-acetylglucosamine (O-GlcNAc) to serine/threonine residues, is a relatively recently identified post-translational modification that has added to the complexity by which protein function is regulated. Two intracellular enzymes, O-GlcNAc transferase and O-GlcNAcase, catalyze the addition and removal, respectively, of O-GlcNAc to serine and threonine side-chain hydroxyl groups. Numerous proteins, including enzymes, transcription factors, receptors and structural proteins have been shown to be modified by intracellular O-glycosylation. In this review, the mechanism and relevance of O-GlcNAc protein modification are discussed in the context of cell adhesion and several representative diseases.