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人类多药耐药相关MVP/LRP基因启动子的克隆及初步分析

Cloning and initial analysis of the human multidrug resistance-related MVP/LRP gene promoter.

作者信息

Lange C, Walther W, Schwabe H, Stein U

机构信息

Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Strasse 10, 13092 Berlin, Germany.

出版信息

Biochem Biophys Res Commun. 2000 Nov 11;278(1):125-33. doi: 10.1006/bbrc.2000.3782.

DOI:10.1006/bbrc.2000.3782
PMID:11071864
Abstract

The lung resistance-related protein (LRP) was identified as the human major vault protein (MVP), and is overexpressed in various multidrug-resistant cancer cell lines and clinical samples. We characterized DNA sequences upstream to the transcription initiation site of the MVP gene in the human non-small cell lung cancer cell line SW-1573. A 1.9-kb and a shortened 0.7-kb fragment of the 5'-upstream genomic region show strong promoter activity in chloramphenicol acetyltransferase (CAT) reporter assays. The promoter is TATA-less and contains an inverted CCAAT-box and a Sp1 site located near to a p53 binding motif. An alternative 3'-splice site of intron 1 results in a splicing variant within the 5'-untranslated region of MVP mRNA.

摘要

肺耐药相关蛋白(LRP)被鉴定为人主要穹窿蛋白(MVP),并在多种多药耐药癌细胞系和临床样本中过度表达。我们对人非小细胞肺癌细胞系SW - 1573中MVP基因转录起始位点上游的DNA序列进行了特征分析。在氯霉素乙酰转移酶(CAT)报告基因检测中,5' - 上游基因组区域的一个1.9 kb片段和一个缩短的0.7 kb片段显示出很强的启动子活性。该启动子无TATA盒,含有一个反向CCAAT盒和一个位于p53结合基序附近的Sp1位点。内含子1的一个可变3' - 剪接位点导致MVP mRNA的5' - 非翻译区内出现一个剪接变体。

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