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Sir2 histone deacetylase prevents programmed cell death caused by sustained activation of the Hog1 stress‐activated protein kinase
Author(s) -
Vendrell Alexandre,
MartínezPastor Mar,
GonzálezNovo Alberto,
PascualAhuir Amparo,
Sinclair David A,
Proft Markus,
Posas Francesc
Publication year - 2011
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2011.154
Subject(s) - microbiology and biotechnology , programmed cell death , histone deacetylase , ubiquitin ligase , reactive oxygen species , kinase , activator (genetics) , apoptosis , protein kinase a , transcription factor , chemistry , biology , histone , biochemistry , ubiquitin , receptor , gene
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.