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首页> 外文期刊>Molecular and Cellular Biology >Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function.
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Differential activation of target cellular promoters by p53 mutants with impaired apoptotic function.

机译：凋亡功能受损的p53突变体对靶细胞启动子的差异激活。

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The p53 tumor suppressor protein is a sequence-specific transcriptional activator, a function which contributes to cell cycle arrest and apoptosis induced by p53 in appropriate cell types. Analysis of a series of p53 point mutants has revealed the potential for selective loss of the ability to transactivate some, but not all, cellular p53-responsive promoters. p53 175P and p53 181L are tumor-derived p53 point mutants which were previously characterized as transcriptionally active. Both mutants retained the ability to activate expression of the cyclin-dependent kinase inhibitor p2lcip1/waf1, and this activity correlated with the ability to induce a G1 cell cycle arrest. However, an extension of this survey to include other p53 targets showed that p53 175P was defective in the activation of p53-responsive sequences derived from the bax promoter and the insulin-like growth factor-binding protein 3 gene (IGF-BP3) promoter, while p53 181L showed loss of the ability to activate a promoter containing IGF-BP3 box B sequences. Failure to activate transcription was also reflected in the reduced ability of the mutants to bind the p53-responsive DNA sequences present in these promoters. These specific defects in transcriptional activation correlated with the impaired apoptotic function displayed by these mutants, and the results suggest that activation of cell cycle arrest genes by p53 can be separated from activation of genes with a role in mediating the p53 apoptotic response. The cellular response to p53 activation may therefore depend, at least in part, on which group of p53-responsive genes become transcriptionally activated.
机译：p53肿瘤抑制蛋白是一种序列特异性转录激活因子，该功能有助于在适当的细胞类型中阻止p53诱导的细胞周期停滞和凋亡。对一系列p53点突变体的分析表明，有可能选择性丧失激活部分而非全部细胞p53反应性启动子的能力。 p53 175P和p53 181L是肿瘤来源的p53点突变体，以前被表征为具有转录活性。这两个突变体都保留了激活细胞周期蛋白依赖性激酶抑制剂p2lcip1 / waf1表达的能力，而这种活性与诱导G1细胞周期停滞的能力有关。但是，此调查的扩展包括其他p53靶标，表明p53 175P在bax启动子和胰岛素样生长因子结合蛋白3基因（IGF-BP3）启动子衍生的p53反应序列的激活中存在缺陷，而p53 181L显示了失去激活包含IGF-BP3 box B序列的启动子的能力。未能激活转录也反映了突变体结合这些启动子中存在的p53反应性DNA序列的能力降低。这些特定的转录激活缺陷与这些突变体显示的凋亡功能受损有关，结果表明，p53对细胞周期阻滞基因的激活可以与介导p53细胞凋亡反应的基因激活分开。因此，对p53激活的细胞应答可以至少部分取决于哪一组p53应答基因被转录激活。

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