Strauss B E, Shivakumar C, Deb S P, Deb S, Haas M
Department of Pathology, University of California, San Diego, La Jolla 92093-0063, USA.
Biochem Biophys Res Commun. 1995 Dec 26;217(3):825-31. 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.
我们研究了野生型p53蛋白与人多药耐药基因-1（MDR1）下游启动子的相互作用。我们的研究结果表明，在BHK和Saos-2细胞系的共转染实验中，野生型p53以剂量依赖的方式抑制由MDR1下游启动子（相对于主要转录起始位点的碱基对-189至+133）驱动的报告基因活性。已从MDR1下游启动子中分离出一段123个碱基对的DNA片段（相对于主要转录起始位点的-119至+4）、一段193个碱基对的片段（-189至+4）和一段135个碱基对的片段（-2至+133），与完整启动子一样，这些片段也受到野生型p53的负调控。此外，我们展示了野生型p53蛋白与MDR1下游启动子的序列特异性结合。这些体外实验结果表明，野生型p53的存在会在转录水平上对MDR1基因产物p-糖蛋白的表达产生负面影响。
