O-GlcNAc and the control of gene expression

Many eukaryotic proteins contain O-linked N-acetylglucosamine (O-GlcNAc) on their serine and threonine side chain hydroxyls. In contrast to classical cell surface glycosylation, O-GlcNAc occurs on resident nuclear and cytopla smic proteins. O-GlcNAc exists as a single monosaccharide residue, showing no evidence of further elongation. Like phosphorylation, O-GlcNAc is highly dynamic, transiently modifying proteins. These post-translational modifica tions give rise to functionally distinct subsets of a given protein. Furthe rmore, all known O-GlcNAc proteins are also phosphoproteins that reversibly form multimeric complexes that are sensitive to the state of phosphorylati on. This observation implies that O-GlcNAc may work in concert with phospho rylation to mediate regulated protein interactions. The proteins that bear the O-GlcNAc modification are very diverse, including RNA polymerase II and many of its transcription factors, numerous chromatin-associated proteins, nuclear pore proteins, proto-oncogenes, tumor suppressors and proteins inv olved in translation. Here, we discuss the functional implications of O-Glc NAc-modifications of proteins involved in various aspects of gene expressio n, beginning with proteins involved in transcription and ending with protei ns involved in regulating protein translation. (C) 1999 Elsevier Science B. V. All rights reserved.