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    Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration.

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    Authors
    Vivancos, Ana P
    Castillo, Esther A
    Jones, Nic
    Ayte, Jose
    Hidalgo, Elena
    Affiliation
    Cell Signalling Unit, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, C/Dr Aiguader 80, E-08003 Barcelona, Spain.
    Issue Date
    2004-06
    
    Metadata
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    Abstract
    The transcription factor Pap1 and the MAP kinase Sty1 are key regulators of hydrogen peroxide-induced responses in Schizosaccharomyces pombe. Pap1 can be activated quickly at low, but not high, hydrogen peroxide concentrations. The MAP kinase Sty1 has been reported to participate in Pap1 activation by the oxidant. Here, we provide biochemical and genetic evidence for the in vivo formation of a hydrogen peroxide-induced disulphide bond in Pap1, which precedes the rapid and reversible nuclear accumulation of the transcription factor. We show that activation of the Sty1 cascade before the oxidative insult, or overexpression of the Sty1-regulated genes ctt1 (encoding catalase) or gpx1 (encoding glutathione peroxidase), can accelerate Pap1 entry even at high doses of hydrogen peroxide. In fact, the lack of Sty1 impedes Pap1 nuclear localization, but only at high doses of the oxidant. We propose that, whereas low doses of hydrogen peroxide lead directly to Pap1 oxidation-activation, high concentrations of the oxidant initially activate the Sty1 pathway, with the consequent increase in scavenging enzymes, which in turn helps to decompose the excess of hydrogen peroxide and achieve an appropriate concentration for the subsequent activation of Pap1. Our results also suggest that activation of Sty1 at high doses of hydrogen peroxide may also be required to trigger other antioxidant activities such as those reverting the overoxidation of cysteine residues at the Pap1 pathway.
    Citation
    Activation of the redox sensor Pap1 by hydrogen peroxide requires modulation of the intracellular oxidant concentration. 2004, 52 (5):1427-35 Mol. Microbiol.
    Journal
    Molecular Microbiology
    URI
    http://hdl.handle.net/10541/78149
    DOI
    10.1111/j.1365-2958.2004.04065.x
    PubMed ID
    15165244
    Type
    Article
    Language
    en
    ISSN
    0950-382X
    ae974a485f413a2113503eed53cd6c53
    10.1111/j.1365-2958.2004.04065.x
    Scopus Count
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    All Paterson Institute for Cancer Research

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