The Brn-3a transcription factor inhibits the pro-apoptotic effect of p53 and enhances cell cycle arrest by differentially regulating the activity of the p53 target genes encoding Bax and p21CIP1/Waf1

被引:47
作者
Budram-Mahadeo, V [1 ]
Morris, PJ [1 ]
Latchman, DS [1 ]
机构
[1] UCL, Inst Child Hlth, Med Mol Biol Unit, London WC1N 1EH, England
基金
英国医学研究理事会;
关键词
Brn-3a; p53; neuronal cells; apoptosis; cell-cycle arrest;
D O I
10.1038/sj.onc.1205842
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
We have previously shown that the anti-apoptotic transcription factor, Brn-3a and the pro-apoptotic p53 factor have antagonistic effects on the promoter of the gene encoding the anti-apoptotic Bcl-2 protein, with p53 abolishing activation by Brn-3a. Here we demonstrate that this antagonism is also observed on the gene encoding the pro-apoptotic Bax protein with Brn-3a abolishing the ability of p53 to activate the Bax promoter and induce Bax protein expression. In contrast, Brn-3a and p53 cooperative to induce maximal activation of another p53 target gene encoding the cyclin dependent kinase inhibitor, p21(CIP1/Waf1). These differential effects of Brn-3a on p53-inducible genes involved in apoptosis or growth arrest are paralleled by its effects on these processes themselves. Thus, we show that Brn-3a antagonises the anti-apoptotic effect of p53 but co-operates with p53 to induce cell cycle arrest. The potential role of Brn-3a in determining the outcome of enhanced p53 levels is discussed.
引用
收藏
页码:6123 / 6131
页数:9
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