O-GlcNAc: a regulatory post-translational modification.

Beta-N-acetylglucosamine (O-GlcNAc) is a regulatory post-translational modification of nuclear and cytosolic proteins. The enzymes for its addition and removal have recently been cloned and partially characterized. While only about 80 mammalian proteins have been identified to date that carry this modification, it is clear that this represents just a small percentage of the modified proteins. O-GlcNAc has all the properties of a regulatory modification including being dynamic and inducible. The modification appears to modulate transcriptional and signal transduction events. There are also accruing data that O-GlcNAc plays a role in apoptosis and neurodegeneration. A working model is emerging that O-GlcNAc serves as a metabolic sensor that attenuates a cell's response to extracellular stimuli based on the energy state of the cell. In this review, we will focus on the enzymes that add/remove O-GlcNAc, the functional impact of O-GlcNAc modification, and the current working model for O-GlcNAc as a nutrient sensor.