Details

Autor(en) / Beteiligte

• Bozonet, Stephanie M
• Findlay, Victoria J
• Day, Alison M
• Cameron, Jannine
• Veal, Elizabeth A
• Morgan, Brian A

Titel

Oxidation of a Eukaryotic 2-Cys Peroxiredoxin Is a Molecular Switch Controlling the Transcriptional Response to Increasing Levels of Hydrogen Peroxide

Ist Teil von

• The Journal of biological chemistry, 2005-06, Vol.280 (24), p.23319-23327

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2005

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 2 O 2 . 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 H 2 O 2 . Furthermore, they reveal that a single eukaryotic 2-Cys Prx regulates peroxide signaling by multiple independent mechanisms.