ABCC4 explained

ATP-binding cassette sub-family C member 4 (ABCC4), also known as the multidrug resistance-associated protein 4 (MRP4) or multi-specific organic anion transporter B (MOAT-B), is a protein that in humans is encoded by the ABCC4 gene.^{[1] [2]}

ABCC4 acts as a regulator of intracellular cyclic nucleotide levels and as a mediator of cAMP-dependent signal transduction to the nucleus.^[3] MRP4/ABCC4 also transports prostaglandins, for example PGE2, out of the cell where they can bind receptors.^[4]

MRP4/ABCC4 expression is dysregulated in several cancers ^{[5] [6] [7]} and is also upregulated in peritoneal endometriosis.^[8]

See also

• ATP-binding cassette transporter

Further reading

• Guey LT, García-Closas M, Murta-Nascimento C, Lloreta J, Palencia L, Kogevinas M, Rothman N, Vellalta G, Calle ML, Marenne G, Tardón A, Carrato A, García-Closas R, Serra C, Silverman DT, Chanock S, Real FX, Malats N . Genetic susceptibility to distinct bladder cancer subphenotypes . European Urology . 57 . 2 . 283–92 . February 2010 . 19692168 . 3220186 . 10.1016/j.eururo.2009.08.001 .
• Rose JE, Behm FM, Drgon T, Johnson C, Uhl GR . Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score . Molecular Medicine . 16 . 7–8 . 247–53 . 2010 . 20379614 . 2896464 . 10.2119/molmed.2009.00159 .
• Rodríguez-Nóvoa S, Labarga P, Soriano V, Egan D, Albalater M, Morello J, Cuenca L, González-Pardo G, Khoo S, Back D, Owen A . Predictors of kidney tubular dysfunction in HIV-infected patients treated with tenofovir: a pharmacogenetic study . Clinical Infectious Diseases . 48 . 11 . e108-16 . June 2009 . 19400747 . 10.1086/598507 . free .
• Holmes MV, Shah T, Vickery C, Smeeth L, Hingorani AD, Casas JP . Fulfilling the promise of personalized medicine? Systematic review and field synopsis of pharmacogenetic studies . PLOS ONE . 4 . 12 . e7960 . 2009 . 19956635 . 2778625 . 10.1371/journal.pone.0007960 . 2009PLoSO...4.7960H . Luo . Yuan . free .
• Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, Kim RB, Tirona RG . Human skeletal muscle drug transporters determine local exposure and toxicity of statins . Circulation Research . 106 . 2 . 297–306 . February 2010 . 19940267 . 10.1161/CIRCRESAHA.109.203596 . free .
• Jedlitschky G, Cattaneo M, Lubenow LE, Rosskopf D, Lecchi A, Artoni A, Motta G, Niessen J, Kroemer HK, Greinacher A . Role of MRP4 (ABCC4) in platelet adenine nucleotide-storage: evidence from patients with delta-storage pool deficiencies . The American Journal of Pathology . 176 . 3 . 1097–103 . March 2010 . 20133816 . 2832132 . 10.2353/ajpath.2010.090425 .
• Saito A, Kawamoto M, Kamatani N . Association study between single-nucleotide polymorphisms in 199 drug-related genes and commonly measured quantitative traits of 752 healthy Japanese subjects . Journal of Human Genetics . 54 . 6 . 317–23 . June 2009 . 19343046 . 10.1038/jhg.2009.31 . free .
• Hosgood HD, Menashe I, He X, Chanock S, Lan Q . PTEN identified as important risk factor of chronic obstructive pulmonary disease . Respiratory Medicine . 103 . 12 . 1866–70 . December 2009 . 19625176 . 2783799 . 10.1016/j.rmed.2009.06.016 .
• Ban H, Andoh A, Imaeda H, Kobori A, Bamba S, Tsujikawa T, Sasaki M, Saito Y, Fujiyama Y . The multidrug-resistance protein 4 polymorphism is a new factor accounting for thiopurine sensitivity in Japanese patients with inflammatory bowel disease . Journal of Gastroenterology . 45 . 10 . 1014–21 . October 2010 . 20393862 . 10.1007/s00535-010-0248-y . 586429 .
• Kucka M, Kretschmannova K, Murano T, Wu CP, Zemkova H, Ambudkar SV, Stojilkovic SS . Dependence of multidrug resistance protein-mediated cyclic nucleotide efflux on the background sodium conductance . Molecular Pharmacology . 77 . 2 . 270–9 . February 2010 . 19903828 . 2812068 . 10.1124/mol.109.059386 .
• Aleksunes LM, Yeager RL, Klaassen CD . Application of multivariate statistical procedures to identify transcription factors that correlate with MRP2, 3, and 4 mRNA in adult human livers . Xenobiotica . 39 . 7 . 514–22 . July 2009 . 19480556 . 2698955 . 10.1080/00498250902952514 .
• Ming X, Thakker DR . Role of basolateral efflux transporter MRP4 in the intestinal absorption of the antiviral drug adefovir dipivoxil . Biochemical Pharmacology . 79 . 3 . 455–62 . February 2010 . 19735648 . 10.1016/j.bcp.2009.08.029 .
• Brüggemann M, Trautmann H, Hoelzer D, Kneba M, Gökbuget N, Raff T . Multidrug resistance-associated protein 4 (MRP4) gene polymorphisms and treatment response in adult acute lymphoblastic leukemia . Blood . 114 . 26 . 5400–1; author reply 5401–2 . December 2009 . 20018925 . 10.1182/blood-2009-09-243741 . free .
• Clemente MI, Alvarez S, Serramía MJ, Turriziani O, Genebat M, Leal M, Fresno M, Muñoz-Fernández MA . Non-steroidal anti-inflammatory drugs increase the antiretroviral activity of nucleoside reverse transcriptase inhibitors in HIV type-1-infected T-lymphocytes: role of multidrug resistance protein 4 . Antiviral Therapy . 14 . 8 . 1101–11 . 2009 . 20032540 . 10.3851/IMP1468 . 30947345 . free .
• Radilova H, Libra A, Holasova S, Safarova M, Viskova A, Kunc F, Buncek M . COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells . Molecular and Cellular Biochemistry . 330 . 1–2 . 131–40 . October 2009 . 19399588 . 10.1007/s11010-009-0126-1 . 25586752 .
• Low SK, Kiyotani K, Mushiroda T, Daigo Y, Nakamura Y, Zembutsu H . Association study of genetic polymorphism in ABCC4 with cyclophosphamide-induced adverse drug reactions in breast cancer patients . Journal of Human Genetics . 54 . 10 . 564–71 . October 2009 . 19696793 . 10.1038/jhg.2009.79 . free .
• Ansari M, Sauty G, Labuda M, Gagné V, Laverdière C, Moghrabi A, Sinnett D, Krajinovic M . Polymorphisms in multidrug resistance-associated protein gene 4 is associated with outcome in childhood acute lymphoblastic leukemia . Blood . 114 . 7 . 1383–6 . August 2009 . 19515727 . 10.1182/blood-2008-11-191098 . free .
• Yuasa I, Umetsu K, Matsusue A, Nishimukai H, Harihara S, Fukumori Y, Saitou N, Jin F, Chattopadhyay PK, Henke L, Henke J . A Japanese-specific allele in the GALNT11 gene . Legal Medicine . 12 . 4 . 208–11 . July 2010 . 20547088 . 10.1016/j.legalmed.2010.04.001 .
• Moyer AM, Sun Z, Batzler AJ, Li L, Schaid DJ, Yang P, Weinshilboum RM . Glutathione pathway genetic polymorphisms and lung cancer survival after platinum-based chemotherapy . Cancer Epidemiology, Biomarkers & Prevention . 19 . 3 . 811–21 . March 2010 . 20200426 . 2837367 . 10.1158/1055-9965.EPI-09-0871 .
• Xu S, Weerachayaphorn J, Cai SY, Soroka CJ, Boyer JL . Aryl hydrocarbon receptor and NF-E2-related factor 2 are key regulators of human MRP4 expression . American Journal of Physiology. Gastrointestinal and Liver Physiology . 299 . 1 . G126-35 . July 2010 . 20395535 . 2904108 . 10.1152/ajpgi.00522.2010 .

Notes and References

1. Web site: Entrez Gene: ATP-binding cassette.
2. Lee K, Belinsky MG, Bell DW, Testa JR, Kruh GD . Isolation of MOAT-B, a widely expressed multidrug resistance-associated protein/canalicular multispecific organic anion transporter-related transporter . Cancer Research . 58 . 13 . 2741–7 . July 1998 . 9661885 .
3. Sassi Y, Lipskaia L, Vandecasteele G, Nikolaev VO, Hatem SN, Cohen Aubart F, Russel FG, Mougenot N, Vrignaud C, Lechat P, Lompré AM, Hulot JS . Multidrug resistance-associated protein 4 regulates cAMP-dependent signaling pathways and controls human and rat SMC proliferation . The Journal of Clinical Investigation . 118 . 8 . 2747–57 . August 2008 . 18636120 . 2467383 . 10.1172/JCI35067 .
4. Reid G, Wielinga P, Zelcer N, van der Heijden I, Kuil A, de Haas M . etal . 2003 . The human multidrug resistanceprotein MRP4 functions as a prostaglandin efflux transporter and is inhibited by nonsteroidal antiinflammatory drugs . Proc Natl Acad Sci U S A . 100 . 16. 9244–9 . 10.1073/pnas.1033060100 . 12835412 . 170903 . 2003PNAS..100.9244R . free .
5. Ho LL, Kench JG, Handelsman DJ, Scheffer GL, Stricker PD, Grygiel JG . etal . 2008 . Androgen regulation of multidrugresistance-associated protein 4 (MRP4/ABCC4) in prostate cancer . Prostate . 68 . 13. 1421–9 . 10.1002/pros.20809 . 18615486 . 42717909 .
6. Copsel S, Garcia C, Diez F, Vermeulem M, Baldi A, Bianciotti LG . etal . 2011 . Multidrug resistance protein 4(MRP4/ABCC4) regulates cAMP cellular levels and controls human leukemia cellproliferation and differentiation . J Biol Chem . 286 . 9. 6979–88 . 10.1074/jbc.m110.166868 . 21205825 . 3044954 . free .
7. Holla VR, Backlund MG, Yang P,Newman RA, DuBois RN. Regulation of prostaglandin transporters in colorectalneoplasia. Cancer Prev Res (Phila). 2008;1(2) 93-9.
8. Gori I, Rodriguez Y, Pellegrini C, Achtari C, Hornung D, Chardonnens E, Wunder D, Fiche M, Canny GO . 2013. Augmented epithelial multidrug resistance-associated protein 4 expression in peritoneal endometriosis: regulation by lipoxin A(4) . Fertil Steril . 99. 7. 1965–1973.e2. 10.1016/j.fertnstert.2013.01.146 . 23472950. free.