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首页> 外文期刊>Molecular and Cellular Biology >Transcriptional activation of the human epidermal growth factor receptor promoter by human p53.
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Transcriptional activation of the human epidermal growth factor receptor promoter by human p53.

机译：人p53对人表皮生长因子受体启动子的转录激活。

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The human epidermal growth factor receptor (EGFR) promoter is activated by both wild-type and tumor-derived mutant p53. In this communication, we demonstrate that EGFR promoter sequence requirements for transactivation by wild-type and mutant p53 are different. Transient-expression assays with EGFR promoter deletions identified a wild-type human p53 response element, 5'-AGCTAGACGTCCGGGCAGCCCCCGGCG -3', from positions --265 to --239. Electrophoretic mobility shift analysis and DNase I footprinting assays indicated that wild-type p53 binds sequence specifically to the response element. Using circularly permuted DNA fragments containing the p53-binding site, we show that wild-type p53 binding induces DNA bending at this site. We further show that the EGFR promoter is also activated by tumor-derived p53 mutants p53-143A, p53-175H, p53-248W, p53-273H, and p53-281G. However, the transactivation by mutant p53 does not require the wild-type p53-binding site. The minimal EGFR promoter from positions --104 to --20 which does not contain the wild-type p53-binding site is transactivated by the p53 mutants but not by the wild-type protein, showing a difference in the mechanism of transactivation by wild-type and mutant p53. Transactivation of the EGFR promoter by p53 may represent a novel mechanism of cell growth regulation.
机译：人类表皮生长因子受体（EGFR）启动子被野生型和肿瘤来源的突变体p53激活。在这种交流中，我们证明了野生型和突变型p53反式激活的EGFR启动子序列要求是不同的。具有EGFR启动子缺失的瞬时表达测定法鉴定了野生型人p53反应元件5'-AGCTAGACGTCCGGGCAGCCCCCGGGG -3'，位置为--265至--239。电泳迁移率变化分析和DNase I足迹分析表明，野生型p53将序列特异性结合到反应元件上。使用包含p53结合位点的圆形排列的DNA片段，我们显示野生型p53结合诱导在该位点的DNA弯曲。我们进一步显示，EGFR启动子也被肿瘤衍生的p53突变体p53-143A，p53-175H，p53-248W，p53-273H和p53-281G激活。但是，突变体p53的反式激活不需要野生型p53结合位点。不包含野生型p53结合位点的--104到--20位的最小EGFR启动子被p53突变体激活，但不被野生型蛋白激活，这表明野生型的激活机制有所不同型和突变型p53。 p53对EGFR启动子的反式激活可能代表了一种新的细胞生长调节机制。

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