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.
Comer
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FI
Department of Biological Chemistry, Johns Hopkins University School of Medicine, 725 N. Wolfe St., Baltimore, MD 21205, USA.
Hart
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GW
D000117:Acetylglucosamine / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D005057:Eukaryotic Cells; D005786:Gene Expression Regulation; D009687:Nuclear Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D010750:Phosphoproteins; D014157:Transcription Factors; D012319:RNA Polymerase II; D000117:Acetylglucosamine