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 cytoplasmic 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 modifications give rise to functionally distinct subsets of a given protein. Furthermore, all known O-GlcNAc proteins are also phosphoproteins that reversibly form multimeric complexes that are sensitive to the state of phosphorylation. This observation implies that O-GlcNAc may work in concert with phosphorylation 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 involved in translation. Here, we discuss the functional implications of O-GlcNAc-modifications of proteins involved in various aspects of gene expression, beginning with proteins involved in transcription and ending with proteins involved in regulating protein translation. (C) 1999 Elsevier Science B.V. All rights reserved.