hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.
hypoxia-inducible factors activate CD133 promoter through ETS family transcription factors.
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DOI：
10.1371/journal.pone.0066255
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Takeda H
中科院分区：
文献类型：
--
作者：
Ohnishi S;Maehara O;Nakagawa K;Kameya A;Otaki K;Fujita H;Higashi R;Takagi K;Asaka M;Sakamoto N;Kobayashi M;Takeda H
CD133是一种细胞表面蛋白，已被报道为癌症干细胞标志物，因此被认为是癌症治疗的潜在靶点。然而，调控CD133表达的机制尚不清楚。在本研究中，我们分析了人胚胎肾（HEK） 293细胞和结肠癌细胞系WiDr中CD133的5个推定启动子（P1-P5）的活性，发现启动子的活性，特别是P5的活性，通过过表达缺氧诱导因子（HIF-1α和HIF-2α）而升高。缺失和突变分析发现，P5区域的两个e - 26 （ETS）结合位点（EBSs）中的一个对于HIF-1α和HIF-2α诱导的启动子活性至关重要。此外，染色质免疫沉淀实验表明HIF-1α和HIF-2α结合到ebs的近端P5启动子上。免疫沉淀实验显示HIF-1α与Elk1有物理相互作用；然而，HIF-2α不与Elk1或ETS1结合。此外，HIF-1α和HIF-2α的下调导致CD133在WiDr中的表达降低。综上所述，我们的研究结果表明HIF-1α和HIF-2α通过ETS蛋白激活CD133启动子。
CD133 is a cellular surface protein that has been reported to be a cancer stem cell marker, and thus it is considered to be a potential target for cancer treatment. However, the mechanism regulating CD133 expression is not yet understood. In this study, we analyzed the activity of five putative promoters (P1–P5) of CD133 in human embryonic kidney (HEK) 293 cells and colon cancer cell line WiDr, and found that the activity of promoters, particularly of P5, is elevated by overexpression of hypoxia-inducible factors (HIF-1α and HIF-2α). Deletion and mutation analysis identified one of the two E-twenty six (ETS) binding sites (EBSs) in the P5 region as being essential for its promoter activity induced by HIF-1α and HIF-2α. In addition, a chromatin imunoprecipitation assay demonstrated that HIF-1α and HIF-2α bind to the proximal P5 promoter at the EBSs. The immunoprecipitation assay showed that HIF-1α physically interacts with Elk1; however, HIF-2α did not bind to Elk1 or ETS1. Furthermore, knockdown of both HIF-1α and HIF-2α resulted in a reduction of CD133 expression in WiDr. Taken together, our results revealed that HIF-1α and HIF-2α activate CD133 promoter through ETS proteins.
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影响因子：
37.3
作者：
Tabu K;Kimura T;Sasai K;Wang L;Bizen N;Nishihara H;Taga T;Tanaka S
通讯作者：
Tanaka S
影响因子：
64.8
作者：
O'Brien, Catherine A.;Pollett, Aaron;Dick, John E.
通讯作者：
Dick, John E.
影响因子：
11.2
作者：
Aprelikova, Olga;Wood, Matthew;Barrett, J. Carl
通讯作者：
Barrett, J. Carl
影响因子：
11.2
作者：
Collins, AT;Berry, PA;Maitland, NJ
通讯作者：
Maitland, NJ
影响因子：
6
作者：
Baba, Yoshifumi;Nosho, Katsuhiko;Ogino, Shuji
通讯作者：
Ogino, Shuji