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Gene Review

ABCB1  -  ATP-binding cassette, sub-family B...

Homo sapiens

Synonyms: ABC20, ATP-binding cassette sub-family B member 1, CD243, CLCS, GP170, ...
 
 
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Disease relevance of ABCB1

 

Psychiatry related information on ABCB1

 

High impact information on ABCB1

  • We describe the general structural and mechanistic features of the human MDR-ABC transporters and introduce some of the basic methods that can be applied for the analysis of their expression, function, regulation, and modulation [16].
  • Often, in cells grown in cell culture, drug resistance correlates with the presence of one or more of the so-called P-glycoproteins or multidrug resistance proteins, products of the mdr family of genes [17].
  • Kinetics of the multidrug transporter (P-glycoprotein) and its reversal [17].
  • Here we report the exclusion of five of these genes and the identification of the first mutations responsible for the development of PXE in a gene encoding a protein associated with multidrug resistance (ABCC6) [18].
  • Multidrug resistance in Yersinia pestis mediated by a transferable plasmid [19].
 

Chemical compound and disease context of ABCB1

 

Biological context of ABCB1

 

Anatomical context of ABCB1

 

Associations of ABCB1 with chemical compounds

  • Intestinal expression of UGT1A1, ABCB1, and ABCC2 was inversely correlated with the effects of ezetimibe on plant sterol serum concentrations [33].
  • The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients [34].
  • LY475776 modulated MRP1 and Pgp-mediated resistance (MDR, ABCB1) in, respectively, HeLa-T5 and CEM/VLB(100) cells to both vincristine and doxorubicin [35].
  • Overall, this study indicates that ABCB1 genotype might be correlated with tipifarnib pharmacokinetics, although considerable overlap in exposure measures between genotype groups was observed [36].
  • Duodenal ABCB1 mRNA content was significantly correlated with the AUC(0-infinity) (r = 0.627, P = 0.039) and C(max) (r = 0.718, P = 0.013) of oral talinolol [37].
  • No association was found between genetic factors and Pgp function using rhodamine 123 accumulation [38].
  • More interestingly, when the cotherapy was combined with the properties of nanoparticle drug delivery, the MDR cells can be resensitized to a dose of paclitaxel near the IC(50) of non-MDR (drug sensitive) cells, indicating a 100-fold increase in chemosensitization via this approach [39].
 

Physical interactions of ABCB1

  • MRP2 transports several anticancer drugs and might thus have a similar impact on chemotherapy as P-gp and BCRP [40].
  • This activity is similar to the multidrug resistance (MDR) activity mediated by ATP binding cassette (ABC) efflux transporters [41].
  • P-glycoprotein (P-gp) is an ideal model protein for studying how mutations disrupt folding of ATP-binding cassette proteins such as CFTR because specific chemical chaperones can be used to correct folding defects [42].
  • Rifampicin has its greatest effects on the pharmacokinetics of orally administered drugs that are metabolised by CYP3A4 and/or are transported by P-glycoprotein [43].
  • The sister gene of P-glycoprotein (Spgp) is a liver-specific ATP-binding cassette protein highly related to the P-glycoprotein (Pgp) family (S. Childs et al, Cancer Res., 55: 2029-2034, 1995) [44].
 

Enzymatic interactions of ABCB1

 

Regulatory relationships of ABCB1

  • MDR1 likely influences basal CYP3A4 expression by limiting the intracellular concentration of an endogenous regulator [47].
  • We measured the kinetics of active efflux of seven new anthracycline derivatives in P-gp-expressing K562/ADR cells and in MRP1-expressing GLC4/ADR cells [48].
  • In normal testis, P-gp and BCRP were strongly expressed by myoid cells and luminal capillary endothelial wall and P-gp also by Leydig cells [49].
  • We have previously demonstrated that proton NMR spectra of fatty acid chains in erythroleukemia K562 wild-type cells and their MDR1 counterparts show variations related to the phenotype over-expressing the P-glycoprotein (P-gp) [50].
  • Recently, it has been demonstrated that in vitro both c-Ha-Ras overexpression and mutant p53 overexpression do activate the MDR1 gene (also known as PGY1) in murine NIH 3T3 cells [4].
 

Other interactions of ABCB1

 

Analytical, diagnostic and therapeutic context of ABCB1

 

References

  1. Loss of detoxification in inflammatory bowel disease: dysregulation of pregnane X receptor target genes. Langmann, T., Moehle, C., Mauerer, R., Scharl, M., Liebisch, G., Zahn, A., Stremmel, W., Schmitz, G. Gastroenterology (2004) [Pubmed]
  2. Breast cancer resistance protein in drug resistance of primitive CD34+38- cells in acute myeloid leukemia. Raaijmakers, M.H., de Grouw, E.P., Heuver, L.H., van der Reijden, B.A., Jansen, J.H., Scheper, R.J., Scheffer, G.L., de Witte, T.J., Raymakers, R.A. Clin. Cancer Res. (2005) [Pubmed]
  3. Genetic variation in ABCB1 influences paclitaxel pharmacokinetics in Japanese patients with ovarian cancer. Yamaguchi, H., Hishinuma, T., Endo, N., Tsukamoto, H., Kishikawa, Y., Sato, M., Murai, Y., Hiratsuka, M., Ito, K., Okamura, C., Yaegashi, N., Suzuki, N., Tomioka, Y., Goto, J. Int. J. Gynecol. Cancer (2006) [Pubmed]
  4. P-glycoprotein, HER-2/neu, and mutant p53 expression in human gynecologic tumors. Schneider, J., Rubio, M.P., Barbazán, M.J., Rodriguez-Escudero, F.J., Seizinger, B.R., Castresana, J.S. J. Natl. Cancer Inst. (1994) [Pubmed]
  5. Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine. Herweijer, H., Sonneveld, P., Baas, F., Nooter, K. J. Natl. Cancer Inst. (1990) [Pubmed]
  6. ABCB1 and GST polymorphisms associated with TP53 status in breast cancer. Nordgard, S.H., Ritchie, M.D., Jensrud, S.D., Motsinger, A.A., Alnaes, G.I., Lemmon, G., Berg, M., Geisler, S., Moore, J.H., Lønning, P.E., Børresen-Dale, A.L., Kristensen, V.N. Pharmacogenet. Genomics (2007) [Pubmed]
  7. Common ABCB1 polymorphisms are not associated with multidrug resistance in epilepsy using a gene-wide tagging approach. Leschziner, G.D., Andrew, T., Leach, J.P., Chadwick, D., Coffey, A.J., Balding, D.J., Bentley, D.R., Pirmohamed, M., Johnson, M.R. Pharmacogenet. Genomics (2007) [Pubmed]
  8. MDR1 diplotypes as prognostic markers in multiple myeloma. Maggini, V., Buda, G., Martino, A., Presciuttini, S., Galimberti, S., Orciuolo, E., Barale, R., Petrini, M., Rossi, A.M. Pharmacogenet. Genomics (2008) [Pubmed]
  9. Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Hung, C.C., Chen, C.C., Lin, C.J., Liou, H.H. Pharmacogenet. Genomics (2008) [Pubmed]
  10. Single nucleotide polymorphisms in the multidrug resistance gene 1 (ABCB1): effects on its expression and clinicopathological characteristics in breast cancer patients. Vaclavikova, R., Nordgard, S.H., Alnaes, G.I., Hubackova, M., Kubala, E., Kodet, R., Mrhalova, M., Novotny, J., Gut, I., Kristensen, V.N., Soucek, P. Pharmacogenet. Genomics (2008) [Pubmed]
  11. ABCB1 (MDR1)-type P-glycoproteins at the blood-brain barrier modulate the activity of the hypothalamic-pituitary-adrenocortical system: implications for affective disorder. Müller, M.B., Keck, M.E., Binder, E.B., Kresse, A.E., Hagemeyer, T.P., Landgraf, R., Holsboer, F., Uhr, M. Neuropsychopharmacology (2003) [Pubmed]
  12. ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients. Frankfort, S.V., Doodeman, V.D., Bakker, R., Tulner, L.R., van Campen, J.P., Smits, P.H., Beijnen, J.H. Molecular neurodegeneration [electronic resource]. (2006) [Pubmed]
  13. Correction of defective protein kinesis of human P-glycoprotein mutants by substrates and modulators. Loo, T.W., Clarke, D.M. J. Biol. Chem. (1997) [Pubmed]
  14. Deposition of Alzheimer's beta-amyloid is inversely correlated with P-glycoprotein expression in the brains of elderly non-demented humans. Vogelgesang, S., Cascorbi, I., Schroeder, E., Pahnke, J., Kroemer, H.K., Siegmund, W., Kunert-Keil, C., Walker, L.C., Warzok, R.W. Pharmacogenetics (2002) [Pubmed]
  15. MDR1 genetic polymorphism does not modify either cell permissiveness to HIV-1 or disease progression before treatment. Bleiber, G., May, M., Suarez, C., Martinez, R., Marzolini, C., Egger, M., Telenti, A. J. Infect. Dis. (2004) [Pubmed]
  16. Human Multidrug Resistance ABCB and ABCG Transporters: Participation in a Chemoimmunity Defense System. Sarkadi, B., Homolya, L., Szak??cs, G., V??radi, A. Physiol. Rev. (2006) [Pubmed]
  17. Kinetics of the multidrug transporter (P-glycoprotein) and its reversal. Stein, W.D. Physiol. Rev. (1997) [Pubmed]
  18. Mutations in a gene encoding an ABC transporter cause pseudoxanthoma elasticum. Le Saux, O., Urban, Z., Tschuch, C., Csiszar, K., Bacchelli, B., Quaglino, D., Pasquali-Ronchetti, I., Pope, F.M., Richards, A., Terry, S., Bercovitch, L., de Paepe, A., Boyd, C.D. Nat. Genet. (2000) [Pubmed]
  19. Multidrug resistance in Yersinia pestis mediated by a transferable plasmid. Galimand, M., Guiyoule, A., Gerbaud, G., Rasoamanana, B., Chanteau, S., Carniel, E., Courvalin, P. N. Engl. J. Med. (1997) [Pubmed]
  20. Response to antiretroviral treatment in HIV-1-infected individuals with allelic variants of the multidrug resistance transporter 1: a pharmacogenetics study. Fellay, J., Marzolini, C., Meaden, E.R., Back, D.J., Buclin, T., Chave, J.P., Decosterd, L.A., Furrer, H., Opravil, M., Pantaleo, G., Retelska, D., Ruiz, L., Schinkel, A.H., Vernazza, P., Eap, C.B., Telenti, A. Lancet (2002) [Pubmed]
  21. Expression of the multidrug resistance associated protein and P-glycoprotein in doxorubicin-selected human myeloid leukemia cells. Slapak, C.A., Mizunuma, N., Kufe, D.W. Blood (1994) [Pubmed]
  22. Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. Bordow, S.B., Haber, M., Madafiglio, J., Cheung, B., Marshall, G.M., Norris, M.D. Cancer Res. (1994) [Pubmed]
  23. Multidrug resistance proteins in gastrointestinal stromal tumors: site-dependent expression and initial response to imatinib. Théou, N., Gil, S., Devocelle, A., Julié, C., Lavergne-Slove, A., Beauchet, A., Callard, P., Farinotti, R., Le Cesne, A., Lemoine, A., Faivre-Bonhomme, L., Emile, J.F. Clin. Cancer Res. (2005) [Pubmed]
  24. Increased MDR1 expression in normal and malignant peripheral blood mononuclear cells obtained from patients receiving depsipeptide (FR901228, FK228, NSC630176). Robey, R.W., Zhan, Z., Piekarz, R.L., Kayastha, G.L., Fojo, T., Bates, S.E. Clin. Cancer Res. (2006) [Pubmed]
  25. ABCB1 and cytochrome P450 genotypes and phenotypes: influence on methadone plasma levels and response to treatment. Crettol, S., Déglon, J.J., Besson, J., Croquette-Krokar, M., Hämmig, R., Gothuey, I., Monnat, M., Eap, C.B. Clin. Pharmacol. Ther. (2006) [Pubmed]
  26. Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics. Niemi, M., Backman, J.T., Kajosaari, L.I., Leathart, J.B., Neuvonen, M., Daly, A.K., Eichelbaum, M., Kivistö, K.T., Neuvonen, P.J. Clin. Pharmacol. Ther. (2005) [Pubmed]
  27. Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel. Henningsson, A., Marsh, S., Loos, W.J., Karlsson, M.O., Garsa, A., Mross, K., Mielke, S., Viganò, L., Locatelli, A., Verweij, J., Sparreboom, A., McLeod, H.L. Clin. Cancer Res. (2005) [Pubmed]
  28. Distribution of breast cancer resistance protein (BCRP/ABCG2) mRNA expression along the human GI tract. Gutmann, H., Hruz, P., Zimmermann, C., Beglinger, C., Drewe, J. Biochem. Pharmacol. (2005) [Pubmed]
  29. Reduction of Cytotoxicity of the Alkaloid Emetine through P-Glycoprotein (MDR1/ABCB1) in Human Caco-2 Cells and Leukemia Cell Lines. M??ller, M., Weiss, J., Wink, M. Planta Med. (2006) [Pubmed]
  30. Single nucleotide polymorphisms in ABCC2 and ABCB1 genes and their clinical impact in physiology and drug response. Wada, M. Cancer Lett. (2006) [Pubmed]
  31. Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Burger, H., van Tol, H., Brok, M., Wiemer, E.A., de Bruijn, E.A., Guetens, G., de Boeck, G., Sparreboom, A., Verweij, J., Nooter, K. Cancer Biol. Ther. (2005) [Pubmed]
  32. Activity of P-glycoprotein in B-cell chronic lymphocytic leukemia determined by a flow cytometric assay. Ludescher, C., Hilbe, W., Eisterer, W., Preuss, E., Huber, C., Gotwald, M., Hofmann, J., Thaler, J. J. Natl. Cancer Inst. (1993) [Pubmed]
  33. Intestinal expression of P-glycoprotein (ABCB1), multidrug resistance associated protein 2 (ABCC2), and uridine diphosphate-glucuronosyltransferase 1A1 predicts the disposition and modulates the effects of the cholesterol absorption inhibitor ezetimibe in humans. Oswald, S., Haenisch, S., Fricke, C., Sudhop, T., Remmler, C., Giessmann, T., Jedlitschky, G., Adam, U., Dazert, E., Warzok, R., Wacke, W., Cascorbi, I., Kroemer, H.K., Weitschies, W., von Bergmann, K., Siegmund, W. Clin. Pharmacol. Ther. (2006) [Pubmed]
  34. The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Haufroid, V., Mourad, M., Van Kerckhove, V., Wawrzyniak, J., De Meyer, M., Eddour, D.C., Malaise, J., Lison, D., Squifflet, J.P., Wallemacq, P. Pharmacogenetics (2004) [Pubmed]
  35. Evaluation of the binding of the tricyclic isoxazole photoaffinity label LY475776 to multidrug resistance associated protein 1 (MRP1) orthologs and several ATP- binding cassette (ABC) drug transporters. Dantzig, A.H., Shepard, R.L., Pratt, S.E., Tabas, L.B., Lander, P.A., Ma, L., Paul, D.C., Williams, D.C., Peng, S.B., Slapak, C.A., Godinot, N., Perry, W.L. Biochem. Pharmacol. (2004) [Pubmed]
  36. Pharmacogenetics of tipifarnib (R115777) transport and metabolism in cancer patients. Sparreboom, A., Marsh, S., Mathijssen, R.H., Verweij, J., McLeod, H.L. Investigational new drugs. (2004) [Pubmed]
  37. Simvastatin does not influence the intestinal P-glycoprotein and MPR2, and the disposition of talinolol after chronic medication in healthy subjects genotyped for the ABCB1, ABCC2 and SLCO1B1 polymorphisms. Bernsdorf, A., Giessmann, T., Modess, C., Wegner, D., Igelbrink, S., Hecker, U., Haenisch, S., Cascorbi, I., Terhaag, B., Siegmund, W. British journal of clinical pharmacology. (2006) [Pubmed]
  38. Sequential influences of leukemia-specific and genetic factors on p-glycoprotein expression in blasts from 817 patients entered into the National Cancer Research Network acute myeloid leukemia 14 and 15 trials. Seedhouse, C.H., Grundy, M., White, P., Li, Y., Fisher, J., Yakunina, D., Moorman, A.V., Hoy, T., Russell, N., Burnett, A., Pallis, M. Clin. Cancer Res. (2007) [Pubmed]
  39. Modulation of intracellular ceramide using polymeric nanoparticles to overcome multidrug resistance in cancer. van Vlerken, L.E., Duan, Z., Seiden, M.V., Amiji, M.M. Cancer Res. (2007) [Pubmed]
  40. MRP2 (ABCC2) transports taxanes and confers paclitaxel resistance and both processes are stimulated by probenecid. Huisman, M.T., Chhatta, A.A., van Tellingen, O., Beijnen, J.H., Schinkel, A.H. Int. J. Cancer (2005) [Pubmed]
  41. Increase in multidrug transport activity is associated with oocyte maturation in sea stars*. Roepke, T.A., Hamdoun, A.M., Cherr, G.N. Dev. Growth Differ. (2006) [Pubmed]
  42. Processing mutations located throughout the human multidrug resistance P-glycoprotein disrupt interactions between the nucleotide binding domains. Loo, T.W., Bartlett, M.C., Clarke, D.M. J. Biol. Chem. (2004) [Pubmed]
  43. Pharmacokinetic interactions with rifampicin : clinical relevance. Niemi, M., Backman, J.T., Fromm, M.F., Neuvonen, P.J., Kivistö, K.T. Clinical pharmacokinetics. (2003) [Pubmed]
  44. Taxol resistance mediated by transfection of the liver-specific sister gene of P-glycoprotein. Childs, S., Yeh, R.L., Hui, D., Ling, V. Cancer Res. (1998) [Pubmed]
  45. Herbal modulation of P-glycoprotein. Zhou, S., Lim, L.Y., Chowbay, B. Drug Metab. Rev. (2004) [Pubmed]
  46. Calpain inhibitor causes accumulation of ubiquitinated P-glycoprotein at the cell surface: possible role of calpain in P-glycoprotein turnover. Ohkawa, K., Asakura, T., Takada, K., Sawai, T., Hashizume, Y., Okawa, Y., Yanaihara, N. Int. J. Oncol. (1999) [Pubmed]
  47. MDR1 genotype is associated with hepatic cytochrome P450 3A4 basal and induction phenotype. Lamba, J., Strom, S., Venkataramanan, R., Thummel, K.E., Lin, Y.S., Liu, W., Cheng, C., Lamba, V., Watkins, P.B., Schuetz, E. Clin. Pharmacol. Ther. (2006) [Pubmed]
  48. Preferential efflux by P-glycoprotein, but not MRP1, of compounds containing a free electron donor amine. Salerno, M., Przewloka, T., Fokt, I., Priebe, W., Garnier-Suillerot, A. Biochem. Pharmacol. (2002) [Pubmed]
  49. The distribution of drug-efflux pumps, P-gp, BCRP, MRP1 and MRP2, in the normal blood-testis barrier and in primary testicular tumours. Bart, J., Hollema, H., Groen, H.J., de Vries, E.G., Hendrikse, N.H., Sleijfer, D.T., Wegman, T.D., Vaalburg, W., van der Graaf, W.T. Eur. J. Cancer (2004) [Pubmed]
  50. Differentiation of the P-gp and MRP1 multidrug resistance systems by mobile lipid 1H-NMR spectroscopy and phosphatidylserine externalization. Mannechez, A., Collet, B., Payen, L., Lecureur, V., Fardel, O., Le Moyec, L., de Certaines, J.D., Leray, G. Anticancer Res. (2001) [Pubmed]
  51. Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. Norris, M.D., Bordow, S.B., Marshall, G.M., Haber, P.S., Cohn, S.L., Haber, M. N. Engl. J. Med. (1996) [Pubmed]
  52. Role of ABCG2/BCRP in biology and medicine. Krishnamurthy, P., Schuetz, J.D. Annu. Rev. Pharmacol. Toxicol. (2006) [Pubmed]
  53. Multidrug resistance and the lung resistance-related protein in human colon carcinoma SW-620 cells. Kitazono, M., Sumizawa, T., Takebayashi, Y., Chen, Z.S., Furukawa, T., Nagayama, S., Tani, A., Takao, S., Aikou, T., Akiyama, S. J. Natl. Cancer Inst. (1999) [Pubmed]
  54. Irinotecan pathway genotype analysis to predict pharmacokinetics. Mathijssen, R.H., Marsh, S., Karlsson, M.O., Xie, R., Baker, S.D., Verweij, J., Sparreboom, A., McLeod, H.L. Clin. Cancer Res. (2003) [Pubmed]
  55. Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Tsuchiya, N., Satoh, S., Tada, H., Li, Z., Ohyama, C., Sato, K., Suzuki, T., Habuchi, T., Kato, T. Transplantation (2004) [Pubmed]
  56. Vincristine transcriptional regulation of efflux drug transporters in carcinoma cell lines. Huang, R., Murry, D.J., Kolwankar, D., Hall, S.D., Foster, D.R. Biochem. Pharmacol. (2006) [Pubmed]
  57. Relationship between the C3435T and G2677T(A) polymorphisms in the ABCB1 gene and P-glycoprotein expression in human liver. Owen, A., Goldring, C., Morgan, P., Chadwick, D., Park, B.K., Pirmohamed, M. British journal of clinical pharmacology. (2005) [Pubmed]
 
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