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.
Strauss
B E
BE
Department of Pathology, University of California, San Diego, La Jolla 92093-0063, USA.
Shivakumar
C
C
Deb
S P
SP
Deb
S
S
Haas
M
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D018432:Drug Resistance, Multiple; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D017931:DNA Primers; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53