Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress. A survival response of mammalian cells

J Biol Chem. 2004 Jul 16;279(29):30133-42. doi: 10.1074/jbc.M403773200. Epub 2004 May 11.


Cellular response to environmental, physiological, or chemical stress is key to survival following injury or disease. Here we describe a unique signaling mechanism by which cells detect and respond to stress in order to survive. A wide variety of stress stimuli rapidly increase nucleocytoplasmic protein modification by O-linked beta-N-acetylglucosamine (O-GlcNAc), an essential post-translational modification of Ser and Thr residues of metazoans. Blocking this post-translational modification, or reducing it, renders cells more sensitive to stress and results in decreased cell survival; and increasing O-GlcNAc levels protects cells. O-GlcNAc regulates both the rates and extent of the stress-induced induction of heat shock proteins, providing a molecular basis for these findings.

Publication types

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

MeSH terms

  • Acetylglucosamine / metabolism*
  • Animals
  • COS Cells
  • Cell Nucleus / metabolism*
  • Cell Survival
  • Cytoplasm / metabolism*
  • Densitometry
  • Dose-Response Relationship, Drug
  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins / metabolism
  • HeLa Cells
  • Heat-Shock Proteins / metabolism
  • Humans
  • Mice
  • Protein Processing, Post-Translational
  • RNA Interference
  • Recombination, Genetic
  • Signal Transduction
  • Temperature
  • Time Factors


  • HSP40 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • Heat-Shock Proteins
  • Acetylglucosamine