Abstract
P-glycoprotein (Pgp), an ATP-dependent efflux transporter that protects the body from environmental toxins and xenobiotics, is encoded by the humanMDR1 gene. HumanMDR1 is located on chromosomal region 7q21. Although several different single nucleotide polymorphisms were shown to influence Pgp expression and activity, the reported length of theMDR1 gene in Genbank and other databases continues to evolve and varies between 6.3 kilobases (kb) and 210 kb. With DNA derived from human cell lines and tissues, we have characterized theMDR1 genomic sequence to be 209 kb.
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Ueda K, Cornwell MM, Gottesman MM, et al. The mdrl gene, responsible for multidrug-resistance, codes for P-glycoprotein.Biochem Biophys Res Commun. 1986;141:956–962.
Borst P, Evers R, Kool M, Wijnholds J. A family of drug transporters: the multidrug resistance-associated protein.J Natl Cancer Inst. 2000;92:1295–1302.
Sakaeda T, Nakamura T, Okumura K. Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmacodynamics of drugs.Pharmacogenomics. 2003;4:397–410.
Woodahl EL, Ho RJ. The role of MDR1 genetic polymorphisms in interindividual variability in P-glycoprotein expression and function.Curr Drug Metab. 2004;5:11–19.
Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter.Annu Rev Biochem. 1993;62:385–427.
Ueda K, Okamura N, Hirai M, et al. Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.J Biol Chem. 1992;267:24248–24252.
Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506.J Biol Chem. 1993;268:6077–6080.
Labialle S, Gayet L, Marthinet E, Rigal D, Baggetto LG. Transcriptional regulation of the humanMDR1 gene at the level of the inverted MED-1 promoter region.Ann NY Acad Sci. 2002;973:468–471.
Mickley LA, Spengler BA, Knutsen TA, Biedler JL, Fojo T. Gene rearrangement: a novel mechanism for MDR-1 gene activation.J Clin Invest. 1997;99:1947–1957.
Ueda K, Clark DP, Chen CJ, Roninson IB, Gottesman MM, Pastan I. The human multidrug resistance (mdr1) gene. cDNA cloning and transcription initiation.J Biol Chem. 1987;262:505–508.
Chen CJ, Clark D, Ueda K, Pastan I, Gottesman MM, Roninson IB. Genomic organization of the human multidrug resistance (MDR1) gene and origin of P-glycoproteins.J Biol Chem. 1990;265:506–514.
INFOBIOGEN [database online]. Evry Cedex, France: Centre de Ressources INFOBIOGEN; 2004. Updated March 2004.
NCBI [database online]. Bethesda, MD: National Center for Biotechnology Information; 2004. Updated March 2004.
Project Ensembl [database online]. Hinxton, UK: The Wellcome Trust Sanger Institute; 2004. Updated March 2004.
Trambas C, Wang Z, Cianfriglia M, Woods G. Evidence that natural killer cells express mini P-glycoproteins but not classic 170 kDa P-glycoprotein.Br J Haematol. 2001;114:177–184.
Kawai K, Kusano I, Ido M, Sakurai M, Shiraishi T, Yatani R. Identification of a P-glycoprotein-related protein (mini-P-glycoprotein) which is overexpressed in multidrug resistant cells.Biochem Biophys Res Commun. 1994;198:804–810.
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Published: February 11, 2005.
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Bodor, M., Kelley, E.J. & Ho, R.J. Characterization of the humanMDR1 gene. AAPS J 7, 1 (2005). https://doi.org/10.1208/aapsj070101
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DOI: https://doi.org/10.1208/aapsj070101