ATF/CREB site mediated transcriptional activation and p53 dependent repression of the cyclin A promoter

被引:49
作者
Desdouets, C
Ory, C
Matesic, G
Soussi, T
Brechot, C
SobczakThepot, J
机构
[1] FAC NECKER,INSERM,U370,F-75742 PARIS 15,FRANCE
[2] INST GENET MOLEC,INSERM,U301,F-75010 PARIS,FRANCE
关键词
cell cycle; cAMP responsive element; gene regulation;
D O I
10.1016/0014-5793(96)00330-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:34 / 38
页数:5
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