title: Dynamic O-GlcNAc modification of nucleocytoplasmic proteins in response to stress. A survival response of mammalian cells.
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 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.
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.
authors.forename: Natasha E
authors.initials: NE
authors.lastname: Zachara
authors.forename: Niall
authors.initials: N
authors.lastname: O'Donnell
authors.forename: Win D
authors.initials: WD
authors.lastname: Cheung
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Mercer
authors.forename: Jamey D
authors.initials: JD
authors.lastname: Marth
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Hart
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000378:metabolism*; D002470:Cell Survival; D003593:Cytoplasm / Q000378:metabolism*; D003720:Densitometry; D004305:Dose-Response Relationship, Drug; D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D011995:Recombination, Genetic; D015398:Signal Transduction; D013696:Temperature; D013997:Time Factors
chemical_list: D050956:HSP40 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D000117:Acetylglucosamine