Sodium salicylate and yeast heat shock gene transcription.
The anti-inflammatory drug sodium salicylate modulates the activity of specific transcription factors in humans. Here we show that salicylate and sorbate, another organic acid, stimulate DNA binding by yeast heat shock transcription factor (HSF) in vivo. Surprisingly, salicylate inhibits heat shock gene transcription even in cells induced by a prior heat shock. This inhibition of transcription occurs at a step after HSF and transcription factor IID binding but before promoter melting by RNA polymerase. Salicylate appears to generate a tight binding but activation-impotent HSF by cytoplasmic acidification, since inhibiting proton efflux from cells triggers this same DNA binding and inhibition of heat shock gene expression.
Giardina
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Section of Biochemistry, Molecular and Cell Biology, Cornell University, Ithaca, New York 14853, USA.
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D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009691:Nucleic Acid Denaturation; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins; D012980:Sodium Salicylate / Q000494:pharmacology*; D013011:Sorbic Acid / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D017931:DNA Primers; D004268:DNA-Binding Proteins; C067168:HSF1 protein, S cerevisiae; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D012980:Sodium Salicylate; D013011:Sorbic Acid