The multidrug resistance protein family.

The human multidrug resistance protein (MRP) family contains at least six members: MRP1, the godfather of the family and well known as the multidrug resistance protein, and five homologs, called MRP2-6. In this review, we summarize what is known about the protein structure, the expression in tissues, the routing in cells, the physiological functions, the substrate specificity, and the role in multidrug resistance of the individual members of the MRP family.

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[2]  Hiroshi Suzuki,et al.  Characterization of the Transport Properties of Cloned Rat Multidrug Resistance-associated Protein 3 (MRP3)* , 1999, The Journal of Biological Chemistry.

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[6]  A. Duncan,et al.  Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. , 1992, Science.

[7]  M. Kool,et al.  Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. , 1997, Cancer research.

[8]  D. Keppler,et al.  Characterization of the human multidrug resistance protein isoform MRP3 localized to the basolateral hepatocyte membrane , 1999, Hepatology.

[9]  D. Keppler,et al.  Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. , 1997, Journal of the American Society of Nephrology : JASN.

[10]  M. Kool,et al.  A mutation in the human canalicular multispecific organic anion transporter gene causes the Dubin‐Johnson syndrome , 1997, Hepatology.

[11]  P. Novikoff,et al.  MRP3, a new ATP-binding cassette protein localized to the canalicular domain of the hepatocyte. , 1999, American journal of physiology. Gastrointestinal and liver physiology.

[12]  Y. Sugiyama,et al.  Functional Analysis of a Canalicular Multispecific Organic Anion Transporter Cloned from Rat Liver* , 1998, The Journal of Biological Chemistry.

[13]  G. Peters,et al.  Antifolate resistance mediated by the multidrug resistance proteins MRP1 and MRP2. , 1999, Cancer research.

[14]  M. Ouellette,et al.  Microbial multidrug-resistance ABC transporters. , 1994, Trends in microbiology.

[15]  G. Tusnády,et al.  Membrane topology distinguishes a subfamily of the ATP‐binding cassette (ABC) transporters , 1997, FEBS letters.

[16]  Y. Sugiyama,et al.  Hepatic expression of multidrug resistance-associated protein-like proteins maintained in eisai hyperbilirubinemic rats. , 1998, Molecular pharmacology.

[17]  N. Dean,et al.  Reduction of expression of the multidrug resistance protein (MRP) in human tumor cells by antisense phosphorothioate oligonucleotides. , 1996, Biochemical pharmacology.

[18]  M. Kool,et al.  Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA. , 1998, The Journal of clinical investigation.

[19]  A. Hutchinson,et al.  Characterization of the human ABC superfamily: isolation and mapping of 21 new genes using the expressed sequence tags database. , 1996, Human molecular genetics.

[20]  J. Testa,et al.  Characterization of MOAT-C and MOAT-D, New Members of the MRP/cMOAT Subfamily of Transporter Proteins , 1999 .

[21]  M. Flens,et al.  Tissue distribution of the multidrug resistance protein. , 1996, The American journal of pathology.

[22]  A. Sartorelli,et al.  Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  N. Ballatori,et al.  Roles of MRP2 and oatp1 in Hepatocellular Export of Reduced Glutathione , 1998, Seminars in liver disease.

[24]  R. Davey,et al.  The anthracycline resistance-associated (ara) gene, a novel gene associated with multidrug resistance in a human leukaemia cell line. , 1996, British Journal of Cancer.

[25]  Y. Sugiyama,et al.  Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats. , 1997, Cancer research.

[26]  N. Doggett,et al.  ARA, a novel ABC transporter, is located at 16p13.1, is deleted in inv(16) leukemias, and is shown to be expressed in primitive hematopoietic precursors. , 1998, Genomics.

[27]  W. Lamers,et al.  Hereditary chronic conjugated hyperbilirubinemia in mutant rats caused by defective hepatic anion transport , 1985, Hepatology.

[28]  D. Keppler,et al.  Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. , 1996, Cancer research.

[29]  M. Kool,et al.  Expression of human MRP6, a homologue of the multidrug resistance protein gene MRP1, in tissues and cancer cells. , 1999, Cancer research.

[30]  D. Keppler,et al.  cDNA Cloning of the Hepatocyte Canalicular Isoform of the Multidrug Resistance Protein, cMrp, Reveals a Novel Conjugate Export Pump Deficient in Hyperbilirubinemic Mutant Rats* , 1996, The Journal of Biological Chemistry.

[31]  G. Tusnády,et al.  Membrane Topology and Glycosylation of the Human Multidrug Resistance-associated Protein (*) , 1996, The Journal of Biological Chemistry.

[32]  R. Flavell,et al.  Evidence that the multidrug resistance protein (MRP) functions as a co-transporter of glutathione and natural product toxins. , 1997, Cancer research.

[33]  N. Saijo,et al.  cDNA cloning of a short type of multidrug resistance protein homologue, SMRP, from a human lung cancer cell line. , 1997, Biochemical and biophysical research communications.

[34]  P. Bosma,et al.  Congenital Jaundice in Rats with a Mutation in a Multidrug Resistance-Associated Protein Gene , 1996, Science.

[35]  T. Uchiumi,et al.  A canalicular multispecific organic anion transporter (cMOAT) antisense cDNA enhances drug sensitivity in human hepatic cancer cells. , 1997, Cancer research.

[36]  R. Evers,et al.  The human multidrug resistance-associated protein functionally complements the yeast cadmium resistance factor 1. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[37]  S. Cole,et al.  Characterization of vincristine transport by the M(r) 190,000 multidrug resistance protein (MRP): evidence for cotransport with reduced glutathione. , 1998, Cancer research.

[38]  K. Ueda,et al.  Anti‐cancer drugs and glutathione stimulate vanadate‐induced trapping of nucleotide in multidrug resistance‐associated protein (MRP) , 1997, FEBS letters.

[39]  Jos H. Beijnen,et al.  Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein , 1997, Nature Medicine.

[40]  T. Voskoglou-Nomikos,et al.  Expression of multidrug resistance protein-related genes in lung cancer: correlation with drug response. , 1999, Clinical cancer research : an official journal of the American Association for Cancer Research.

[41]  T. Ishikawa,et al.  Coordinated Induction of MRP/GS-X Pump and γ-Glutamylcysteine Synthetase by Heavy Metals in Human Leukemia Cells* , 1996, The Journal of Biological Chemistry.

[42]  T. Ishikawa,et al.  Glutathione-associated cis-diamminedichloroplatinum(II) metabolism and ATP-dependent efflux from leukemia cells. Molecular characterization of glutathione-platinum complex and its biological significance. , 1993, The Journal of biological chemistry.

[43]  R. Evers,et al.  Canalicular multispecific organic anion transporter/multidrug resistance protein 2 mediates low-affinity transport of reduced glutathione , 1999 .

[44]  F. Baas,et al.  Analysis of the expression of MRP, the gene for a new putative transmembrane drug transporter, in human multidrug resistant lung cancer cell lines. , 1993, Cancer research.

[45]  P. Borst,et al.  Homozygous disruption of the murine MDR2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease , 1993, Cell.

[46]  D. Bell,et al.  Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter. , 1998, Cancer research.

[47]  N. Ballatori,et al.  ATP-dependent Transport of Reduced Glutathione on YCF1, the Yeast Orthologue of Mammalian Multidrug Resistance Associated Proteins* , 1998, The Journal of Biological Chemistry.

[48]  G. Peters,et al.  MRP3, an organic anion transporter able to transport anti-cancer drugs. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[49]  A. Broeks,et al.  Homologues of the human multidrug resistance genes MRP and MDR contribute to heavy metal resistance in the soil nematode Caenorhabditis elegans. , 1996, The EMBO journal.

[50]  D. Keppler,et al.  ATP-dependent transport of bilirubin glucuronides by the multidrug resistance protein MRP1 and its hepatocyte canalicular isoform MRP2. , 1997, The Biochemical journal.

[51]  D. Keppler,et al.  Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. , 1999, Molecular pharmacology.