title: Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high-mobility group protein B1.
abstract: 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.
authors.affiliation: Department of Molecular Biology, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shiota
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Naoya
authors.initials: N
authors.lastname: Miyamoto
authors.forename: Takamitsu
authors.initials: T
authors.lastname: Onitsuka
authors.forename: Eiji
authors.initials: E
authors.lastname: Kashiwagi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kidani
authors.forename: General
authors.initials: G
authors.lastname: Hirano
authors.forename: Mayu
authors.initials: M
authors.lastname: Takahashi
authors.forename: Mayumi
authors.initials: M
authors.lastname: Ono
authors.forename: Michihiko
authors.initials: M
authors.lastname: Kuwano
authors.forename: Seiji
authors.initials: S
authors.lastname: Naito
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.forename: Kimitoshi
authors.initials: K
authors.lastname: Kohno
mesh_terms: D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007624:KB Cells; D008297:Male; D054464:Peroxiredoxins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000473:pathology; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; D050783:Proto-Oncogene Proteins c-ets; C515940:PRDX1 protein, human; C515974:PRDX5 protein, human; D054464:Peroxiredoxins