Dynamic interplay between O-glycosylation and O-phosphorylation of nucleocytoplasmic proteins: a new paradigm for metabolic control of signal transduction and transcription.
The glycosylation of serine and threonine residues with beta-O-linked N-acetylglucosamine (O-GlcNAc) is an abundant posttranslational modification of nuclear and cytoplasmic proteins in multicellular eukaryotes. This highly dynamic glycosylation/deglycosylation of protein is catalyzed by the nucleocytoplasmic enzymes, UDP-G1cNAc: polypeptide O-beta-N-acetylglucosaminyltransferase (OGT)/O-beta-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/or protein function by dynamic glycosylation/phosphorylation has been hypothesized. In this chapter, we will review the current status of dynamic glycosylation/phosphorylation of several important regulatory proteins including c-Myc, estrogen receptors, Sp1, endothelial nitric oxide synthase, and beta-catenin. Various aspects of subcellular localization, association with binding partners, activity, and/or turnover of these proteins appear to be regulated by dynamic glycosylation/ phosphorylation in response to cellular signals or stages.
Kamemura
Kazuo
K
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Hart
Gerald W
GW
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008954:Models, Biological; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D016271:Proto-Oncogene Proteins c-myc; D011960:Receptors, Estrogen; D016329:Sp1 Transcription Factor; D015534:Trans-Activators; D051176:beta Catenin; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III