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Eukaryotic Cell, August 2007, p. 1373-1379, Vol. 6, No. 8
1535-9778/07/$08.00+0 doi:10.1128/EC.00098-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.
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Hiroshi Sakurai*
Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942, Japan
Received 28 March 2007/ Accepted 6 June 2007
The heat shock transcription factor Hsf1 of the yeast Saccharomyces cerevisiae regulates the transcription of a set of genes that contain heat shock elements (HSEs) in their promoters and function in diverse cellular processes, including protein folding. Here, we show that Hsf1 activates the transcription of various target genes when cells are treated with oxidizing reagents, including the superoxide anion generators menadione and KO2 and the thiol oxidants diamide and 1-chloro-2,4-dinitrobenzene (CDNB). Similar to heat shock, the oxidizing reagents are potent inducers of both efficient HSE binding and extensive phosphorylation of Hsf1. The inducible phosphorylation of Hsf1 is regulated by the intramolecular domain-domain interactions and affects HSE structure-specific transcription. Unlike the heat shock, diamide, or CDNB response, menadione or KO2 activation of Hsf1 is inhibited by cyclic-AMP-dependent protein kinase (PKA) activity, which negatively regulates the activator functions of other transcriptional regulators implicated in the oxidative stress response. These results demonstrate that Hsf1 is a member of the oxidative stress-responsive activators and that PKA is a general negative regulator in the superoxide anion response.
Published ahead of print on 22 June 2007.
Supplemental material for this article may be found at http://ec.asm.org/.
Present address: Department of Life Science, Faculty of Science, Okayama University of Science, Okayama 700-0005, Japan.
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