Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress-activated protein kinase

EMBO Rep. 2011 Sep 30;12(10):1062-8. doi: 10.1038/embor.2011.154.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis* / genetics
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • DNA-Binding Proteins / metabolism
  • F-Box Proteins / genetics
  • F-Box Proteins / metabolism
  • Gene Expression
  • Gene Expression Regulation, Fungal
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mutation / genetics
  • Nicotinamidase / genetics
  • Nicotinamidase / metabolism
  • Reactive Oxygen Species / metabolism
  • SKP Cullin F-Box Protein Ligases / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sirtuin 2 / metabolism*
  • Stress, Physiological*
  • Transcription Factors / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism


  • CDC4 protein, S cerevisiae
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • F-Box Proteins
  • MSN2 protein, S cerevisiae
  • Reactive Oxygen Species
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases
  • HOG1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases
  • Sirtuin 2
  • Nicotinamidase
  • PNC1 protein, S cerevisiae