Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high-mobility group protein B1
Ets regulates peroxiredoxin1 and 5 expressions through their interaction with the high-mobility group protein B1
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DOI：
10.1111/j.1349-7006.2008.00912.x
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发表时间：
2008-10-01
期刊：
影响因子：
5.7
通讯作者：
Kohno, Kimitoshi
中科院分区：
文献类型：
--
作者：
Shiota, Masaki;Izumi, Hiroto;Kohno, Kimitoshi
过氧化物酶（Peroxiredoxins，Prdxs）是一种巯基特异性抗氧化蛋白，在人类癌细胞中高度表达。已显示Prdxs在微环境应激（例如缺氧）条件下参与肿瘤细胞增殖。我们假设Prdxs可以分为两组，应激诱导型和非诱导型。在这项研究中，我们分析了五个Prdx家族成员在人类癌细胞中的启动子活性和表达水平。我们发现，Prdx 1和Prdx 5都是诱导后处理过氧化氢或缺氧，但Prdx 2，Prdx 3，和Prdx 4是不是或只是边缘诱导。我们还发现Ets转录因子是胁迫诱导表达的关键激活因子。高迁移率族蛋白HMGB 1通过与Ets转录因子直接相互作用而发挥共激活剂的作用。Ets转录因子的DNA结合被HMGB 1显著增强。Ets 1、Ets 2、Prdx 1和Prdx 5表达的沉默使细胞对氧化应激敏感。这些数据表明，由Ets/HMG蛋白介导的Prdx基因的转录可能保护细胞免受氧化应激。（Cancer Sci 2008; 99：1950-1959）
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. (Cancer Sci 2008; 99: 1950-1959)