Flaman J M, Robert V, Lenglet S, Moreau V, Iggo R, Frebourg T
Laboratoire de Génétique Moléculaire, CHU de Rouen, France.
Oncogene. 1998 Mar 12;16(10):1369-72. doi: 10.1038/sj.onc.1201889.
Recent studies have suggested that a rare class of p53 mutants found in tumours has a subtle transcriptional defect affecting bax induction but not p21 induction. We have therefore developed simple functional assays in yeast which can be used to identify these mutants. Analysis of 51 different mutations observed in human tumours showed that all mutants tested scored as mutant with the bax reporter strain but nine scored as wild-type with the p21 reporter strain. These results, which can be explained by the lower affinity of the p53 protein for the bax site, may suggest that p21 is not the key target of p53 mutations in tumours. Since p21 status has recently been shown to modulate the chemotherapeutic and radiotherapeutic sensitivities of cancerous cells, the functional assays described here may have important clinical implications.
最近的研究表明，在肿瘤中发现的一类罕见的p53突变体存在细微的转录缺陷，影响bax的诱导，但不影响p21的诱导。因此，我们在酵母中开发了简单的功能检测方法，可用于识别这些突变体。对在人类肿瘤中观察到的51种不同突变的分析表明，所有测试的突变体在bax报告菌株中被判定为突变体，但有9种在p21报告菌株中被判定为野生型。这些结果可以用p53蛋白对bax位点的亲和力较低来解释，这可能表明p21不是肿瘤中p53突变的关键靶点。由于最近已表明p21状态可调节癌细胞的化疗和放疗敏感性，这里描述的功能检测方法可能具有重要的临床意义。
