Additive effect between NF-kappa B subunits and p53 protein for transcriptional activation of human p53 promoter

The tumor suppressor p53 plays a pivotal role in the cellular response to D NA damage as it controls DNA repair, cell cycle arrest and apoptosis, We st udied the autoregulation of human p53 gene transcription in colon cancer ce ll lines. Wild-type p53 has been show positively or negatively and probably in a cell-type-specific manner. Indeed, a p53 binding site has been descri bed in the human and murine p53 promoters, but a direct binding of wild-typ e p53 protein to this site has never been reported. In this study, we demon strated a transactivation of human p53 pn to autoregulate its own transcrip tion either promoter by wild-type p53 in human colon cancer cells. We ident ified in the human p53 promoter a novel potential p53-responsive element th at binds wildtype p53. Moreover, wild-type p53 protein transactivated a rep orter plasmid containing a luciferase gene driven by a minimal promoter har boring this p53 binding site. Finally, as the p53 promoter contains an NF-k appa B binding site, we demonstrated an additive effect when NF-kappa B sub units and p53 protein combined to transactivate the human p53 promoter.