title: Nucleocytoplasmic O-glycosylation: O-GlcNAc and functional proteomics.
abstract: The molecular complexity that defines different cell types and their biological responses occurs at the level of the cell's proteome. The recent increase in availability of genomic sequence information is a valuable tool for the field of proteomics. While most proteomic studies focus on differential expression levels, post-translational modifications such as phosphorylation, glycosylation, and acetylation, provide additional levels of functional complexity to the cell's proteome. The reversible post-translational modification O-linked beta-N-acetylglucosamine (O-GlcNAc) is found on serines and threonines of nuclear and cytoplasmic proteins. It appears to be as widespread as phosphorylation. While phosphorylation is recognized as a fundamental mechanism for controlling protein function, less is known about the specific roles of O-GlcNAc modification. However, evidence is building that O-GlcNAc may compete with phosphate at some sites of attachment. Aberrant O-GlcNAc modification has been linked to several disease states, including diabetes and Alzheimer's disease. Regulated enzymes catalyzing the addition (O-GlcNAc transferase, OGT) and removal (O-GlcNAcase) of the modification have been cloned and OGT is required for life at the single cell level. Here we review the properties of O-GlcNAc that suggest it is a regulatory modification analogous to phosphorylation. We also discuss the use of comparative functional proteomics to elucidate functions for this ubiquitous intracellular carbohydrate modification.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: K
authors.initials: K
authors.lastname: Vosseller
authors.forename: L
authors.initials: L
authors.lastname: Wells
authors.forename: G W
authors.initials: GW
authors.lastname: Hart
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D020543:Proteome / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D004791:Enzyme Inhibitors; D009687:Nuclear Proteins; D020543:Proteome; D017351:N-Acetylglucosaminyltransferases; D005947:Glucose; D000117:Acetylglucosamine