Nucleocytoplasmic O-glycosylation: O-GlcNAc and functional proteomics

The molecular complexity that defines different cell types and their biolog ical responses occurs at the level of the cell's proteome. The recent incre ase 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 phosphorylatio n, glycosylation, and acetylation, provide additional levels of functional complexity to the cell's proteome. The reversible post-translational modifi cation O-linked beta -N-acetylglucosaniine (O-GleNAc) is found on serines a nd threonines. of nuclear and cytoplasmic proteins, It appears to be as wid espread as phosphorylation. While phosphorylation is recognized as a fundam ental mechanism for controlling protein function, less is known about the s pecific 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 d iabetes and Alzheimer's disease. Regulated enzymes catalyzing the addition (O-GlcNAc transferase, OGT) and removal (O-GlcNAcase) of the modification h ave 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 modif ication analogous to phosphorylation. We also discuss the use of comparativ e functional proteomics to elucidate functions for this ubiquitous intracel lular carbohydrate modification. (C) 2001 Societe francaise de biochimie et biologic moleculaire / Editions scientifiques et medicales Elsevier SAS. A ll rights reserved.