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首页> 外文期刊>The FEBS journal >Sp1-like sequences mediate human caspase-3 promoter activation by p73 and cisplatin
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Sp1-like sequences mediate human caspase-3 promoter activation by p73 and cisplatin

机译：Sp1样序列介导p73和顺铂激活人caspase-3启动子

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摘要

Caspase-3 is a cysteine protease that plays a central role in the execution of apoptosis induced by a wide variety of stimuli. However, little is known about the mechanisms involved in the regulation of caspase-3 gene transcription. This study was carried out to characterize the human caspase-3 promoter and to understand the mechanisms involved in the induction of caspase-3 gene expression in response to the anticancer drug cisplatin and p73. Caspase-3 gene expression was induced by treatment of cells with cisplatin, which also induced p73 protein in HeLa and K562 cells. The human caspase-3 promoter was cloned and characterized. p73 beta strongly activated the caspase-3 promoter, whereas p73 alpha showed less activation. Cisplatin treatment increased caspase-3 promoter activity. Basal and cisplatin-induced promoter activity was inhibited by the p73 inhibitor p73DD. Deletion analysis defined a minimal promoter of 120 base pairs, which showed good basal and p73 beta-induced activity. The examination of the minimal promoter sequence showed several putative Sp1 sites, but no p53/p73 site. The caspase-3 promoter was activated by Sp1 in Sp1-deficient Drosophila SL-2 cells. Sp1-induced promoter activity was further enhanced by p73 beta in SL-2 cells. Mutation of Sp1 sites in the minimal promoter resulted in a loss of basal and p73-induced promoter activity. These results show that caspase-3 gene transcription is induced by cisplatin, which is mediated partly by p73. We have identified p73 and Sp1 as activators of the caspase-3 promoter. Sp1-like sequences in the minimal promoter not only sustain basal promoter activity, but also mediate p73-induced activation of the promoter.
机译：Caspase-3是一种半胱氨酸蛋白酶，在多种刺激诱导的细胞凋亡执行中起着核心作用。但是，有关caspase-3基因转录调控的机制知之甚少。进行了这项研究以表征人类caspase-3启动子，并了解诱导caspase-3基因表达对抗癌药物顺铂和p73的应答所涉及的机制。通过用顺铂处理细胞来诱导Caspase-3基因表达，顺铂还可以在HeLa和K562细胞中诱导p73蛋白。克隆并表征了人caspase-3启动子。 p73 beta强烈激活caspase-3启动子，而p73 alpha显示较少的激活。顺铂处理增加了caspase-3启动子的活性。 p73抑制剂p73DD抑制了基础和顺铂诱导的启动子活性。缺失分析限定了120个碱基对的最小启动子，其显示了良好的基础和p73β诱导的活性。最小启动子序列的检查显示了几个推定的Sp1位点，但没有p53 / p73位点。在Sp1缺失的果蝇SL-2细胞中，Sp1激活了caspase-3启动子。在SL-2细胞中，p73 beta进一步增强了Sp1诱导的启动子活性。最小启动子中Sp1位点的突变导致基础和p73诱导的启动子活性丧失。这些结果表明，caspase-3基因的转录是由顺铂诱导的，其部分是由p73介导的。我们已经确定p73和Sp1为caspase-3启动子的激活剂。最小启动子中的Sp1样序列不仅维持基础启动子活性，而且介导p73诱导的启动子激活。

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