Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins:: A new paradigm for metabolic control of signal transcluction and transcription

The glycosylation of serine and threonine residues with β-O-linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification of nuclear and cytoplasmic proteins in multicellular eukaryotes. This highly dynamic glycosylation(plus 45 degree rule)deglycosylation of protein is catalyzed by the nucleocytoplasmic enzymes, UDP-GlcNAc: polypeptide O-β-N-acetylglucosaminyltransferase (OGT)(plus 45 degree rule)O-β-N-acetylglucosaminidase. OGT is required for embryonic stem cell viability and mouse ontogeny, thus O-GlcNAc is essential for the life of eukaryotes. The gene encoding O-GlcNAcase maps to a locus important to late-onset Alzheimer's disease. All known O-GlcNAc-modified proteins are also phosphoproteins that form reversible multimeric protein complexes. There is both a global and often site-specific reciprocal relationship between O-GlcNAc and O-phosphate in many cellular responses to stimuli. Thus, regulation of the protein-protein interaction(s) and(plus 45 degree rule)or protein function by dynamic glycosylation(plus 45 degree rule)phosphorylation has been hypothesized. In this chapter, we will review the current status of dynamic glycosylation(plus 45 degree rule)phosphorylation of several important regulatory proteins including c-Myc, estrogen receptors, Sp1, endothelial nitric oxide synthase, and β-catenin. Various aspects of subcellular localization, association with binding partners, activity, and(plus 45 degree rule)or turnover of these proteins appear to be regulated by dynamic glycosylation(plus 45 degree rule)phosphorylation in response to cellular signals or stages. © 2003, Elsevier Science (USA). © 2003 Elsevier Science (USA). All rights reserved.