Negative regulation of the heat shock transcription factor by protein kinase A in Saccharomyces cerevisiae

TL;DRAbstract

Hsf1, the heat shock transcription factor from Saccharomyces cerevisiae, has a low level of constitutive transcriptional activity and is kept in this state through negative regulation. In an effort to understand this negative regulation, I developed a novel genetic selection that detects altered expression from the HSP26 promoter. Using this reporter strain, we identified mutations and dosage compensators in the Ras/cAMP signaling pathway that decrease cAMP levels and increase expression from the HSP26 promoter. In yeast, low cAMP levels reduce the catalytic activity of the cAMP-dependent kinase, PKA. Previous studies had proposed that the stress response transcription factors Msn2/4, but not Hsf1, are repressed by PKA. However, I found that reduction or elimination of PKA activity strongly derepresses transcription of the small heat shock genes HSP26 and HSP12, even in the absence of MSN2/4. In a strain deleted for MSN2/4 and the PKA catalytic subunits, expression of HSP12 and HSP26 d

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