ATF/CREB site mediated transcriptional activation and p53 dependent repression of the cyclin A promoter
ATF/CREB site mediated transcriptional activation and p53 dependent repression of the cyclin A promoter
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DOI：
10.1016/0014-5793(96)00330-4
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发表时间：
1996-04-29
期刊：
影响因子：
3.5
通讯作者：
SobczakThepot, J
中科院分区：
文献类型：
--
作者：
Desdouets, C;Ory, C;SobczakThepot, J
细胞周期蛋白 A 是一种关键调节蛋白，在哺乳动物细胞中参与细胞周期的 S 期。人类细胞周期蛋白 A 基因的转录是通过对其启动子的严格控制来调节细胞周期的。我们之前已经证明，细胞周期蛋白 A 启动子中存在的 ATF/CREB 位点通过 cAMP 响应元件结合蛋白介导转录调节。本研究的主要目的是调查该位点是否参与该基因的转录调控。我们构建了稳定的 NIH-3T3 细胞系，该细胞系在正常或突变版本的细胞周期蛋白 A 启动子的控制下表达荧光素酶报告基因。我们表明，从 G1 晚期开始，细胞周期蛋白 A 启动子的转录需要 ATF/CREB 才能达到最大水平。我们还表明，p53 对细胞周期蛋白 A 启动子的下调并不意味着 p53 与其同源共有序列直接结合，而可能是通过干扰反式激活因子而发生的。这一结果表明，在启动子中不存在 TATA 序列的情况下，p53 可以干扰细胞周期蛋白 A 基因的转录。
Cyclin A is a pivotal regulatory protein which, in mammalian cells, is involved in the S phase of the cell cycle. Transcription of the human cyclin A gene is cell cycle regulated through tight control of its promoter. We have previously shown that the ATF/CREB site, present in the cyclin A promoter, mediates transcriptional regulation by cAMP responsive element binding proteins. The main goal of the present study was to investigate whether this site is involved in transcriptional regulation of the gene. We have constructed stable NIH-3T3 cell lines that express the luciferase reporter gene under the control of normal or mutated versions of the cyclin A promoter. We show that the ATF/CREB is required to achieve maximal levels of transcription from the cyclin A promoter starting in late G1. We also show that down-regulation of the cyclin A promoter by p53 does not implicate a direct binding of p53 to its cognate consensus sequence but occurs probably by interference with trans-activating factors. This result suggests that p53 can interfere with transcription of the cyclin A gene, in the absence of a TATA sequence in the promoter.