Ionizing radiation-inducible apoptosis in the absence of p53 linked to transcription factor EGR-1
Ionizing radiation-inducible apoptosis in the absence of p53 linked to transcription factor EGR-1
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DOI：
10.1074/jbc.272.52.33056
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发表时间：
1997-12-26
影响因子：
4.8
通讯作者：
Rangnekar, VM
中科院分区：
文献类型：
--
作者：
Ahmed, MM;Sells, SF;Rangnekar, VM
肿瘤抑制蛋白p53是细胞凋亡的关键调节因子，缺乏p53蛋白的前列腺癌细胞对电离辐射引起的细胞凋亡具有中度抗性。编码转录因子早期生长反应-1（EGR-1）和细胞因子肿瘤坏死因子-α（TNF-α）的基因在照射前列腺癌细胞后被诱导，EGR-1功能的抑制导致TNF-α诱导和凋亡的消除。电离辐射和EGR-1对TNF-α基因的诱导通过TNF-α启动子中富含GC的EGR-1结合蛾介导。由于TNF-α诱导前列腺癌细胞凋亡，这些发现表明，在p53的情况下，电离辐射诱导的凋亡是由EGR-1介导的TNF-α反式激活。
The tumor suppressor protein p53 is a pivotal regulator of apoptosis, and prostate cancer cells that lack p53 protein are moderately resistant to apoptotic death by ionizing radiation. Genes encoding the transcription factor early growth response-1 (EGR-1) and cytokine tumor necrosis factor-alpha (TNF-alpha) were induced upon irradiation of prostate cancer cells, and inhibition of EGR-1 function resulted in abrogation of both TNF-alpha induction and apoptosis. Induction of the TNF-alpha gene by ionizing radiation and EGR-1 was mediated via a GC-rich EGR-1-binding moth in the TNF-alpha promoter. Because TNF-alpha induces apoptosis in prostate cancer cells, these findings suggest that, in the absence of p53, ionizing radiation-inducible apoptosis is mediated by EGR-1 via TNF-alpha transactivation.