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MBC in Press, published online ahead of print March 7, 2002
Mol. Biol. Cell 10.1091/mbc.01-06-0288

A more recent version of this article appeared on March 1, 2002
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Submitted on June 11, 2001
Revised on October 16, 2001
Accepted on December 12, 2001

Distinct regulatory proteins control the graded transcriptional response to increasing H2O2 levels in the fission yeast, S. pombe

Janet Quinn1, Victoria J. Findlay1, Keren Dawson2, Jonathan B.A. Millar3, Nic Jones2, Brian A. Morgan1, and W. Mark Toone2*

1 School of Biochemistry and Genetics, The Medical School, University of Newcastle, Newcastle-upon-Tyne NE2 4HH, UK
2 CRC Cell Regulation Group, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Rd., Manchester M20 4BX, UK
3 Division of Yeast Genetics, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

* Corresponding author. E-mail address: mtoone{at}PICR.man.ac.uk.

The signaling pathways that sense adverse stimuli and communicate with the nucleus to initiate appropriate changes in gene expression are central to the cellular stress response. Here, we have characterized the role of the Sty1 (Spc1) stress-activated MAPK pathway, and the Pap1 and Atf1 transcription factors, in regulating the response to H2O2 in the fission yeast, Schizosaccharomyces pombe. We find that H2O2 activates the Sty1 pathway in a dose-dependent manner via at least two sensing mechanisms. At relatively low levels of H2O2, a two component-signaling pathway, which feeds into either of the two stress-activated MAPKKKs, Wak1 or Win1, regulates Sty1 phosphorylation. In contrast, at high levels of H2O2, Sty1 activation is controlled predominantly by a two-component independent mechanism and requires the function of both Wak1 and Win1. Individual transcription factors were also found to function within a limited range of H2O2 concentrations. Pap1 activates target genes primarily in response to low levels of H2O2 while Atf1 primarily controls the transcriptional response to high concentrations of H2O2. Our results demonstrate that S. pombe uses a combination of stress responsive regulatory proteins to gauge and effect the appropriate transcriptional response to increasing concentrations of H2O2.




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