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

Natasha E. Zachara, Niall O'Donnell, Win D. Cheung, Jessica J. Mercer, Jamey D. Marth, Gerald W. Hart

Research output: Contribution to journalArticlepeer-review

Abstract

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 β-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.

Original languageEnglish (US)
Pages (from-to)30133-30142
Number of pages10
JournalJournal of Biological Chemistry
Volume279
Issue number29
DOIs
StatePublished - Jul 16 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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