Abstract
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 co-operative 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects*
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Blotting, Western
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Cell Cycle / drug effects
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Cells, Cultured
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins / genetics
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Cyclins / metabolism*
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DNA-Binding Proteins / pharmacology*
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Flow Cytometry
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Genes, p53 / physiology
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Humans
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Luciferases / genetics
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Luciferases / metabolism
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Promoter Regions, Genetic
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Transcription Factor Brn-3
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Transcription Factor Brn-3A
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Transcription Factors / pharmacology*
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Tumor Suppressor Protein p53 / antagonists & inhibitors*
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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Cyclins
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DNA-Binding Proteins
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POU4F1 protein, human
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Transcription Factor Brn-3
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Transcription Factor Brn-3A
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Transcription Factors
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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Luciferases