Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high-mobility group protein B1

Peroxiredoxins (Prdxs) are thiol-specific antioxidant proteins that are highly expressed in human cancer cells. Prdxs have been shown to be involved in tumor cell proliferation under conditions of microenvironmental stress such as hypoxia. We hypothesized that Prdxs could be categorized into two groups, stress-inducible and non-inducible ones. In this study, we analyzed the promoter activity and expression levels of five Prdx family members in human cancer cells. We found that both Prdx1 and Prdx5 are inducible after treatment with hydrogen peroxide or hypoxia, but that Prdx2, Prdx3, and Prdx4 are not or are only marginally inducible. We also found that Ets transcription factors are the key activators for stress-inducible expression. High-mobility group protein HMGB1 was shown to function as a coactivator through direct interactions with Ets transcription factors. The DNA binding of Ets transcription factors was significantly enhanced by HMGB1. Silencing of Ets1, Ets2, Prdx1, and Prdx5 expression sensitized cells to oxidative stress. These data indicate that transcription of Prdx genes mediated by Ets/HMG proteins might protect cells from oxidative stress.