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

Prog Nucleic Acid Res Mol Biol. 2003;73:107-36. doi: 10.1016/s0079-6603(03)01004-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism*
  • Cytoskeletal Proteins / metabolism
  • Glycosylation
  • Humans
  • Models, Biological
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proto-Oncogene Proteins c-myc / metabolism
  • Receptors, Estrogen / metabolism
  • Signal Transduction*
  • Sp1 Transcription Factor / metabolism
  • Trans-Activators / metabolism
  • Transcription, Genetic*
  • beta Catenin


  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins c-myc
  • Receptors, Estrogen
  • Sp1 Transcription Factor
  • Trans-Activators
  • beta Catenin
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III