title: The Skn7 response regulator of Saccharomyces cerevisiae interacts with Hsf1 in vivo and is required for the induction of heat shock genes by oxidative stress.
abstract: The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein-protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and in vivo and we show that Skn7 can bind to the same regulatory sequences as Hsf1, namely heat shock elements. Furthermore, we demonstrate that a strain deleted for the SKN7 gene and containing a temperature-sensitive mutation in Hsf1 is hypersensitive to oxidative stress. Our data suggest that Skn7 and Hsf1 cooperate to achieve maximal induction of heat shock genes in response specifically to oxidative stress. We further show that, like Hsf1, Skn7 can interact with itself and is localized to the nucleus under normal growth conditions as well as during oxidative stress.
authors.affiliation: Division of Yeast Genetics, National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom. desmond_raitt@dfci.harvard.edu
authors.forename: D C
authors.initials: DC
authors.lastname: Raitt
authors.forename: A L
authors.initials: AL
authors.lastname: Johnson
authors.forename: A M
authors.initials: AM
authors.lastname: Erkine
authors.forename: K
authors.initials: K
authors.lastname: Makino
authors.forename: B
authors.initials: B
authors.lastname: Morgan
authors.forename: D S
authors.initials: DS
authors.lastname: Gross
authors.forename: L H
authors.initials: LH
authors.lastname: Johnston
mesh_terms: D000251:Adenosine Triphosphatases; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D018869:Heat-Shock Response; D006361:Heating; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007763:Lac Operon; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C067168:HSF1 protein, S cerevisiae; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C083962:SKN7 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D000251:Adenosine Triphosphatases; C095973:SSA1 protein, S cerevisiae