The MDR1 Downstream Promoter Contains Sequence-Specific Binding Sites for Wild-Type p53

We have examined the interaction of the wild-type p53 protein with the downstream promoter of the human multidrug resistance gene-1 (MDR1). Our findings indicate that wild type p53 inhibits reporter activity driven by the MDR1 downstream promoter (base pairs −189 to +133 relative to the major transcriptional initiation site) in a dose-dependent manner in cotransfection assays in the BHK and the Saos-2 cell lines. A 123 base-pair segment of DNA (−119 to +4 relative to the major transcriptional initiation site), a 193 base-pair segment (−189 to +4), and a 135 base-pair segment (−2 to +133) have been isolated from the MDR1 downstream promoter which, like the full promoter, are negatively controlled by wild-type p53. In addition, we show sequence-specific binding of wild-type p53 protein to the MDR1 downstream promoter. These in vitro results suggest that the presence of wild-type p53 negatively affects expression of the MDR1 gene product, p-glycoprotein, at the transcriptional level.