p300/CBP-dependent and -independent transcriptional interference between NF-kappa B RelA and p53

p53 and NF-kappa B RelA are activated by various genotoxic agents and mutua lly suppress each other's ability to activate transcription, most likely th rough competition for transcriptional coactivators such as CBP or p300. How ever, we found that the inhibition by RelA of p53 transcriptional activity is not completely restored by CBP/p300 overexpression and that a p53 mutant can not suppress RelA activity despite of its ability to bind CBP/p300. In the present study, we further present evidence that these two transcriptio nal factors directly interact both in vivo and in vitro. These results ther efore indicate that the cross transcriptional interference between p53 and RelA is partly caused by the direct interaction between these two transcrip tion factors which is mediated by their dimerization/tetramerization domain s and results in inhibition of each other's transcriptional activity. Final ly, cells derived from RelA knockout mice showed enhanced p53 transcription al activity, suggesting that this cross transcriptional interference is phy siologically important in cellular response to genotoxic stress. (C) 2000 A cademic Press.