Diverse regulation of protein function by O-GlcNAc: a nuclear and cytoplasmic carbohydrate post-translational modification

N-Acetylglucosamine O-linked to serines and threonines of cytosolic and nuclear proteins (O-GlcNAc) is an abundant reversible post-translational modification found in all higher eukaryotes. Evidence for functional regulation of proteins by this dynamic saccharide is rapidly accumulating. Deletion of the gene encoding the enzyme that attaches O-GlcNAc ( OGT) is lethal at the single cell level, indicating the fundamental requirement for this modification. Recent studies demonstrate a role for O-GlcNAcylation in processes as diverse as transcription in the nucleus and signaling in the cytoplasm, suggesting that O-GlcNAc has both protein and site-specific influences on biochemistry and metabolism throughout the cell. It is clearer than ever that the dynamic enzyme-catalyzed chemical modification of polypeptides adds a critical level of complexity and regulation to the cell's proteome. In addition to phosphorylation, post-translational modifications such as acetylation and methylation are now known to control protein function in response to cell stimuli.