title: Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase.
abstract: Exposure of yeast to high osmolarity induces a transient activation of the Hog1 stress-activated protein kinase (SAPK), which is required for cell survival under these conditions. However, sustained activation of the SAPK results in a severe growth defect. We found that prolonged SAPK activation leads to cell death, which is not observed in nma111 cells, by causing accumulation of reactive oxygen species (ROS). Mutations of the SCF(CDC4) ubiquitin ligase complex suppress cell death by preventing the degradation of Msn2 and Msn4 transcription factors. Accumulation of Msn2 and Msn4 leads to the induction of PNC1, which is an activator of the Sir2 histone acetylase. Sir2 is involved in protection against Hog1-induced cell death and can suppress Hog1-induced ROS accumulation. Therefore, cell death seems to be dictated by the balance of ROS induced by Hog1 and the protective effect of Sir2.
authors.affiliation: Cell Signaling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona E-08003, Valencia, Spain.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vendrell
authors.forename: Mar
authors.initials: M
authors.lastname: Martínez-Pastor
authors.forename: Alberto
authors.initials: A
authors.lastname: González-Novo
authors.forename: Amparo
authors.initials: A
authors.lastname: Pascual-Ahuir
authors.forename: David A
authors.initials: DA
authors.lastname: Sinclair
authors.forename: Markus
authors.initials: M
authors.lastname: Proft
authors.forename: Francesc
authors.initials: F
authors.lastname: Posas
mesh_terms: D017209:Apoptosis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015966:Gene Expression Regulation, Fungal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009154:Mutation / Q000235:genetics; D009535:Nicotinamidase / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000378:metabolism*; D013312:Stress, Physiological; D014157:Transcription Factors / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: C080443:CDC4 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D044783:F-Box Proteins; C081935:MSN2 protein, S cerevisiae; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D056565:Sirtuin 2; D009535:Nicotinamidase; C474330:PNC1 protein, S cerevisiae