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

• Published in: Biochemical and biophysical research communications 1995-12, Vol.217 (3), p.825-831
• Main Authors: Strauss, B.E., Shivakumar, C., Deb, S.P., Deb, S., Haas, M.
• Format: Article
• Language: English
• Subjects: ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; Base Sequence; Binding Sites; DNA Primers - chemistry; DNA-Binding Proteins - metabolism; Drug Resistance, Multiple; Gene Expression Regulation; Humans; Molecular Sequence Data; Promoter Regions, Genetic; RNA, Messenger - genetics; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1995.2846

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.