QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 19, Issue 1, 308-317, January 2008

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E07-08-0735v1 19/1/308    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, D. Articles by Bähler, J. Search for Related Content PubMed PubMed Citation Articles by Chen, D. Articles by Bähler, J.

Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast

Dongrong Chen^*,,, Caroline R.M. Wilkinson^,, Stephen Watt^*, Christopher J. Penkett^*,, W. Mark Toone^,||, Nic Jones, and Jürg Bähler^*

*Cancer Research UK Fission Yeast Functional Genomics Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, United Kingdom; and Paterson Institute for Cancer Research, University of Manchester, Manchester M20 4BX, United Kingdom

Submitted August 2, 2007; Revised October 24, 2007; Accepted November 1, 2007
Monitoring Editor: Jonathan Weissman

Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1–like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.

These authors contributed equally to this work.

Present addresses: EMBL Outstation-Hinxton, European Bioinformatics Institute, Cambridge CB10 1SD, United Kingdom;

^|| Samuel Lunenfeld Research Institute, Toronto, Ontario, M5G 1X5, Canada.

Address correspondence to: Jürg Bähler (jurg{at}sanger.ac.uk)

Abbreviations used: CESR, core environmental stress response; HP, hydrogen peroxide; Md, menadione (Md); TBH, t-butylhydroperoxide; MAPK, mitogen-activated protein kinase; ROS, reactive oxygen species; TF, transcription factor.

This article has been cited by other articles:

				T. Udagawa, N. Nemoto, C. R. M. Wilkinson, J. Narashimhan, L. Jiang, S. Watt, A. Zook, N. Jones, R. C. Wek, J. Bahler, et al. Int6/eIF3e Promotes General Translation and Atf1 Abundance to Modulate Sty1 MAPK-dependent Stress Response in Fission Yeast J. Biol. Chem., August 8, 2008; 283(32): 22063 - 22075. [Abstract] [Full Text] [PDF]