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

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.