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首页> 外文期刊>Molecular and Cellular Biology >A mutant p53 that discriminates between p53-responsive genes cannot induce apoptosis.
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A mutant p53 that discriminates between p53-responsive genes cannot induce apoptosis.

机译：区分p53反应基因的突变p53不能诱导细胞凋亡。

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Human wild-type (wt) p53 can induce apoptosis in transiently transfected H1299 cells maintained at 37 degrees C, whereas tumor-derived mutant forms of p53 (with the mutation Ala-143, His-175, or Trp-248) fail to do so. At 37 degrees C, p53 with a mutation to Ala at amino acid 143 (p53Ala143) was transcriptionally inactive. However, at 32 degrees C, p53Ala143 strongly activated transcription from several physiologically relevant p53-responsive promoters, to extents similar or greater than that of wt p53. Unexpectedly, p53Ala143 was defective in inducing apoptosis in H1299 cells at 32 degrees C. Concomitantly with the loss of apoptotic activity, p53Ala143 was found to be deficient in its ability to activate transcription from the p53-responsive portions of the Bax and insulin-like growth factor-binding protein 3 gene promoters. It is proposed that there may exist distinct classes of p53-responsive promoters, whose ability to be activated by p53 can be regulated differentially. Such differential regulation may have functional consequences for the effects of p53 on cell fate.
机译：人类野生型（wt）p53可在维持37摄氏度的瞬时转染的H1299细胞中诱导凋亡，而肿瘤衍生的p53突变形式（具有Ala-143，His-175或Trp-248突变）却无法做到所以。在37摄氏度时，在143位氨基酸处突变为Ala的p53（p53Ala143）在转录上无活性。但是，在32摄氏度下，p53Ala143强烈激活了几个生理相关的p53反应性启动子的转录，其转录程度与wt p53相似或更高。出乎意料的是，p53Ala143在32°C下诱导H1299细胞凋亡方面存在缺陷。伴随凋亡活性的丧失，p53Ala143被发现缺乏激活Bax p53反应部分转录和胰岛素样生长的能力。因子结合蛋白3基因启动子。提出可能存在不同类别的p53应答性启动子，其被p53激活的能力可以被不同地调节。这种差异调节可能会对p53对细胞命运的影响产生功能性后果。

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