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Non-p53 p53RE binding protein a human transcription factor functionally analogous to P53

机译:非p53 p53RE结合蛋白功能类似P53的人类转录因子

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摘要

The transactivation activity of the p53 tumor suppressor protein is critical for regulating cell growth and apoptosis. We describe the identification of a transcription factor that is functionally similar to p53 and contains the same DNA binding and transcription activities specific for the p53 responsive DNA element (p53RE). This protein was highly purified through chromatography from HeLa cell extracts. The purified protein was able to bind specifically to the p53RE derived from a p21waf1 promoter and to stimulate p53RE-dependent transcription but not basal transcription in vitro. Its DNA-binding activity was inhibited by the wild type but not mutant p53RE-containing DNA oligomers. Also, this p53RE-binding activity was found in human p53 null Saos-2 osteosarcoma and H1299 small cell lung carcinoma cells. Interestingly, this activity exhibited a p53RE sequence preference that was distinct from the p53 protein. The activity is neither p53 nor p73, because anti-p53 or anti-73 antibodies were unable to detect this purified protein nor were the antibodies able to alter the p53-like activity, the p53RE-protein complex. These results demonstrate that, besides p73, an additional p53-like protein exists in cells, which is named NBP for non-p53, p53RE binding protein.
机译:p53肿瘤抑制蛋白的反式激活活性对于调节细胞生长和凋亡至关重要。我们描述了一种转录因子的鉴定,该转录因子在功能上类似于p53,并包含对p53反应性DNA元件(p53RE)特定的相同DNA结合和转录活性。该蛋白通过色谱法从HeLa细胞提取物中进行了高度纯化。纯化的蛋白能够与源自p21 waf1 启动子的p53RE特异性结合,并在体外刺激p53RE依赖性转录,但不能刺激基础转录。它的DNA结合活性被野生型抑制,而突变的含p53RE的DNA寡聚体则不被抑制。同样,在人p53缺失的Saos-2骨肉瘤和H1299小细胞肺癌细胞中发现了这种p53RE结合活性。有趣的是,这种活性表现出不同于p53蛋白的p53RE序列偏好。该活性既不是p53也不是p73,因为抗p53或抗73抗体无法检测到这种纯化的蛋白质,而且该抗体也不能改变p53样活性即p53RE蛋白复合物。这些结果表明,除p73外,细胞中还存在另外的p53样蛋白,其被称为非p53,p53RE结合蛋白的NBP。

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