O-GlcNAc a sensor of cellular state: the role of nucleocytoplasmic glycosylation in modulating cellular function in response to nutrition and stress

Biochim Biophys Acta. 2004 Jul 6;1673(1-2):13-28. doi: 10.1016/j.bbagen.2004.03.016.


Myriad nuclear and cytoplasmic proteins in metazoans are modified on Ser and Thr residues by the monosaccharide O-linked beta-N-acetylglucosamine (O-GlcNAc). The rapid and dynamic change in O-GlcNAc levels in response to extracellular stimuli, morphogens, the cell cycle and development suggests a key role for O-GlcNAc in signal transduction pathways. Modulation of O-GlcNAc levels has profound effects on the functioning of cells, in part mediated through a complex interplay between O-GlcNAc and O-phosphate. In many well-studied proteins, the O-GlcNAc modification and phosphorylation are reciprocal. That is, they occur on different subsets of the protein population, as the site of attachment occurs on the same or adjacent Ser/Thr residues. Recently, O-GlcNAc has been implicated in the etiology of type II diabetes, the regulation of stress response pathways, and in the regulation of the proteasome.

Publication types

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

MeSH terms

  • Acetylglucosamine / metabolism*
  • Acetylglucosaminidase / metabolism*
  • Animals
  • Cell Death
  • Cell Nucleus / metabolism*
  • Cytoplasm / metabolism*
  • Diabetes Mellitus, Type 2 / etiology
  • Glucose / metabolism
  • Glycosylation
  • Histone Acetyltransferases
  • Humans
  • Multienzyme Complexes
  • Nutritional Physiological Phenomena
  • Phosphorylation
  • Proteins / metabolism*
  • Signal Transduction*
  • Stress, Physiological / metabolism
  • beta-N-Acetylhexosaminidases


  • Multienzyme Complexes
  • Proteins
  • Histone Acetyltransferases
  • hexosaminidase C
  • Acetylglucosaminidase
  • beta-N-Acetylhexosaminidases
  • Glucose
  • Acetylglucosamine