The MDR1 downstream promoter contains sequence-specific binding sites for wild-type p53

Biochem Biophys Res Commun. 1995 Dec 26;217(3):825-31. doi: 10.1006/bbrc.1995.2846.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily 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*

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • DNA Primers
  • DNA-Binding Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53