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Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch controlling the transcriptional response to increasing levels of hydrogen peroxide

Lookup NU author(s): Stephanie Bozonet, Victoria Findlay, Dr Alison Day, Jannine Cameron, Dr Elizabeth Veal, Professor Brian Morgan

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Abstract

Although activation of the AP-1-like transcription factor Pap1 in Schizosaccharomyces pombe is important for oxidative stress-induced gene expression, this activation is delayed at higher concentrations of peroxide. Here, we reveal that the 2-Cys peroxiredoxin (2-Cys Prx) Tpx1 is required for the peroxide-induced activation of Pap1. Tpx1, like other eukaryotic 2-Cys Prxs, is highly sensitive to oxidation, which inactivates its thioredoxin peroxidase activity. Our data suggest that the reduced thioredoxin peroxidase-active form of Tpx1 is required for the peroxide-induced oxidation and nuclear accumulation of Pap1. Indeed, in contrast to the previously described role for Tpx1 in the activation of the Sty1 stress-activated protein kinase by peroxide, we find that both catalytic cysteines of Tpx1 are required for Pap1 activation. Moreover, overexpression of the conserved sulfiredoxin Srx1, which interacts with and reduces Tpx1, allows rapid activation of Pap1 at higher concentrations of H 2O2. Conversely, loss of Srx1 prevents the reduction of oxidized Tpx1 and prolongs the inhibition of Pap1 activation. Collectively, these data suggest that redox regulation of the thioredoxin peroxidase activity of Tpx1 acts as a molecular switch controlling the transcriptional response to H2O2. Furthermore, they reveal that a single eukaryotic 2-Cys Prx regulates peroxide signaling by multiple independent mechanisms. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.


Publication metadata

Author(s): Bozonet SM, Findlay VJ, Day AM, Cameron J, Veal EA, Morgan BA

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2005

Volume: 280

Issue: 24

Pages: 23319-23327

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.M502757200

DOI: 10.1074/jbc.M502757200

PubMed id: 15824112


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