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Cellular and Molecular Biology Letters

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Volume 19, Issue 1

Yeast ABC proteins involved in multidrug resistance

Agata Piecuch / Ewa Obłąk
Published Online: 2014-03-26 | DOI: https://doi.org/10.2478/s11658-013-0111-2


Pleiotropic drug resistance is a complex phenomenon that involves many proteins that together create a network. One of the common mechanisms of multidrug resistance in eukaryotic cells is the active efflux of a broad range of xenobiotics through ATP-binding cassette (ABC) transporters. Saccharomyces cerevisiae is often used as a model to study such activity because of the functional and structural similarities of its ABC transporters to mammalian ones. Numerous ABC transporters are found in humans and some are associated with the resistance of tumors to chemotherapeutics. Efflux pump modulators that change the activity of ABC proteins are the most promising candidate drugs to overcome such resistance. These modulators can be chemically synthesized or isolated from natural sources (e.g., plant alkaloids) and might also be used in the treatment of fungal infections. There are several generations of synthetic modulators that differ in specificity, toxicity and effectiveness, and are often used for other clinical effects.

Keywords: ABC proteins; PDR subfamily; Saccharomyces cerevisiae; Multidrug resistance; Regulation of ABC proteins; Transcription factors; P-glycoprotein; Modulators of ABC proteins; Flavonoids; Phenothiazines

  • [1] Bauer, B.E., Wolfger, H. and Kuchler, K. Inventory and function of yeast ABC proteins: about sex, stress, pleiotropic drug and heavy metal resistance. Biochim. Biophys. Acta 1461 (1999) 217–236. Google Scholar

  • [2] Jungwirth, H. and Kuchler, K. Yeast ABC transporters — a tale of sex, drugs and aging. FEBS Lett. 580 (2006) 1131–1138. Google Scholar

  • [3] Paumi, C.M., Chuck, M., Snider, J., Stagljar, I. and Michaelis, S. ABC transporters in Saccharomyces cerevisiae and their interactors: new technology advances in the biology of the ABCC (MRP) subfamily. Microbiol. Mol. Biol. Rev. 73 (2009) 577–593. CrossrefGoogle Scholar

  • [4] Rutledge, R.M., Esser, L., Ma, J. and Xia, D. Toward understanding the mechanism of action of the yeast multidrug resistance transporter Pdr5p: a molecular modeling study. J. Struct. Biol. 173 (2011) 333–344. Google Scholar

  • [5] Rogers, B., Decottignies, A., Kolaczkowski, M., Carvajal, E., Balzi, E. and Goffeau, A. The pleiotropic drug ABC transporters from Saccharomyces cerevisiae. J. Mol. Microbiol. Biotechnol. 3 (2001) 207–214. Google Scholar

  • [6] Falcao, A.S., Bellarosa, C., Fernandes, A., Brito, M.A., Silva, R.F.M., Tiribelli, C. and Brites, D. Role of multidrug resistance-associated protein 1 expression in the in vitro susceptibility of rat nerve cell to unconjugated bilirubin. Neuroscience 144 (2007) 878–888. Google Scholar

  • [7] Hwang, T.-C. and Sheppard, D.N. Gating of the CFTR Cl- channel by ATP-driven nucleotide-binding domain dimerisation. J. Physiol. 587 (2009) 2151–2161. Google Scholar

  • [8] Kuchler, K., Sterne, R.E. and Thorner, J. Saccharomyces cerevisiae STE6 gene product: a novel pathway fro protein export in eukaryotic cells. EMBO J. 8 (1989) 3973–1984. Google Scholar

  • [9] Chloupkova, M., LeBard, L.S. and Koeller, D.M. MDL1 is a high copy suppressor of ATM1: evidence for a role in resistance to oxidative stress. J. Mol. Biol. 331 (2003) 155–165. Google Scholar

  • [10] Young, L., Leonhard, K., Tatsuta, T., Trowsdale, J. and Langer, T. Role of the ABC transporter Mdl1 in peptide export from mitochondria. Science 291 (2001) 2135–2138. Google Scholar

  • [11] Lockshon, D., Surface, L.E., Kerr, E.O., Kaeberlein, M. and Kennedy, B.K. The sensitivity of yeast mutants to oleic acid implicates the peroxisome and other processes in membrane function. Genetics 175 (2007) 77–91. Google Scholar

  • [12] Yoshikawa, K., Tanaka, T., Furusawa, C., Nagahisa, K., Hirasawa, T. and Shimisu, H. Comprehensive phenotypic analysis for identification of genes affecting growth under etanol stress in Saccharomyces cerevisiae. FEMS Yeast Res. 9 (2009) 32–44. CrossrefGoogle Scholar

  • [13] Chen, C.-A. and Cowan, J.A. Characterization of Saccharomyces cerevisiae Atm1p: functional studies of an ABC7 type transporter. Biochim. Biophys. Acta 1760 (2006) 1857–1865. Google Scholar

  • [14] Katzmann, D.J., Hallstrom, T.C., Voet, M., Wysock, W., Golin, J., Volcaert, G. and Moye-Rowley, W.S. Expression of an ATP-binding cassette transporterencoding gene (YOR1) is required for oligomycin resistance in Saccharomyces cerevisiae. Mol. Cell. Biol. 15 (1995) 6875–6883. Google Scholar

  • [15] Cui, Z., Hirata, D., Tsuchiya, E., Osada, H. and Miyakawa, T. The multidrug resistance-associated protein (MRP) subfamily (Yrs1/Yor1) of Saccharomyces cerevisiae is important for the tolerance to a broad range of organic anions. J. Biol. Chem. 271 (1996) 14712–14716. Google Scholar

  • [16] Gueldry, O., Lazard, M., Delort, F., Dauplais, M., Grigoras, I., Blanquet, S. and Plateau, P. Ycf1-dependent Hg (II) detoxification in Saccharomyces cerevisiae. Eur. J. Biochem. 270 (2003) 2486–2496. Google Scholar

  • [17] Lazard, M., Ha-Duong, N.T., Mounie, S., Perrin, R., Plateau, P. and Blanquet, S. Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p. FEBS J. 278 (2011) 4112–4121. Google Scholar

  • [18] Ortiz, D.F., St. Pierre, M.V., Abdulmessih, A. and Arias, I.M. A yeast ATPbinding cassette-type protein mediating ATP-dependent bile acid transport. J. Biol. Chem. 272 (1997) 15358–15365. CrossrefGoogle Scholar

  • [19] Klein, M., Mamnun, Y.M., Eggmann, T., Schuller, C., Wolfger, H., Martinoia, E. and Kuchler, K. The ATP-binding cassette (ABC) transporter Bpt1p mediates vacuolar sequestration of glutathione conjugates in yeast. FEBS Lett. 520 (2002) 63–67. Google Scholar

  • [20] Petrovic S., Pascolo, L., Gallo, R., Cupelli, F., Ostrow, J.D., Goffeau, A., Tiribelli, C. and Bruschi, C.V. The products of YCF1 and YLL015w (BPT1) cooperate for the ATP-dependent vacuolar transport of unconjugated bilirubin in Saccharomyces cerevisiae. Yeast 16 (2000) 561–571. CrossrefGoogle Scholar

  • [21] Wawrzycka, D., Sobczak, I., Bartosz, G., Bocer, T., Ułaszewski, S. and Goffeau, A. Vmr1p is a novel vacuolar multidrug resistance ABC transporter in Saccharomyces cerevisiae. FEMS Yeast Res. 10 (2010) 828–838. CrossrefGoogle Scholar

  • [22] Mason, D.L., Mallampalli, M.P., Huyer, G. and Michealis, S. A region within a lumenal loop of Saccharomyces cerevisiae Ycf1p directs proteolytic processing and substrate specifity. Eukaryot. Cell 2 (2003) 588–598. CrossrefGoogle Scholar

  • [23] Hettema, E.H., van Roermund, C.W.T., Distel, B., van den Berg, M., Vilela, C., Rodrigues-Pousada, C., Wanders, R.J.A. and Tabak, H.F. The ABC transporter proteins Pat1 and Pat2 are required for import of long-chain fatty acids into peroxisomes of Saccharomyces cerevisiae. EMBO J. 15 (1996) 3813–3822. Google Scholar

  • [24] Swartzman, E.E., Viswanathan, M.N. and Thorner, J. The PAL1 gene product is a peroxisomal ATP-binding cassette transporter in the yeast Saccharomyces cerevisiae. J. Cell Biol. 132 (1996) 549–563. Google Scholar

  • [25] Sarthy, A.V., McGonigal, T., Capobianco, J.O., Schmidt, M., Green, S.R., Moehle, C.M. and Glodman, R.C. Identification and kinetic analysis of a functional homolog of elongation factor 3, YEF3 in Saccharomyces cerevisiae. Yeast 14 (1998) 239–253. CrossrefGoogle Scholar

  • [26] Sandbaken, M.G., Lupisella, J.A., DiDomenico, B. and Chakraburtty, K. Protein synthesis in yeast. Structural and functional analysis of the gene encoding elongation factor 3. J. Biol. Chem. 265 (1990) 15838–15844. Google Scholar

  • [27] Maurice, T.C., Mazzucco, C.E., Ramanathan, C.S., Ryan, B.M., Warr, G.A. and Puziss, J.W. A highly conserved intraspecies homolog of the Saccharomyces cerevisiae elongation factor-3 encoded by the HEF3 gene. Yeast 14 (1998) 1105–1113. Google Scholar

  • [28] Garcia-Barrio, M., Dong, J., Ufano, S. and Hinnebusch, A.G. Association of GCN1-GCN20 regulatory complex with the N-terminus of elF2α kinase GCN2 is required for GCN2 activation. EMBO J. 19 (2000) 1887–1899. CrossrefGoogle Scholar

  • [29] Sattlegger, E. and Hinnebusch, A.G. Polyribosome binding by GCN1 is required for full activation of eukaryotic translation initiation factor2{alpha} kinase GCN2 during amino acid starvation. J. Biol. Chem. 280 (2005) 16514–16521. Google Scholar

  • [30] Shenton, D., Smirnova, J.B., Selley, J.N., Carroll, K., Hubbard, S.J., Pavitt, G.D., Ashe, M.P. and Grant, C.M. Global translational responses to oxidative stress impact upon multiple levels of protein synthesis. J. Biol. Chem. 281 (2006) 29011–29021. Google Scholar

  • [31] Dong, J., Lai, R., Jennings, J.L., Link, A.J. and Hinnebusch, A.G. The novel ATP-binding cassette protein ARB1 is a shuttling factor that stimulates 40S and 60S ribosome biogenesis. Mol. Cell. Biol. 25 (2005) 9859–9873. CrossrefGoogle Scholar

  • [32] Li, Z., Lee, I., Moradi, E., Hung, N.J., Johnson, A.W. and Marcotte, E.M. Rational extension of the ribosome biogenesis pathway using networkguided genetics. PLoS Biol. 7 (2009) e1000213. CrossrefGoogle Scholar

  • [33] Khoshnevis, S., Gross, T., Rotte, C., Baierlein, C., Ficner, R. and Krebber, H. The iron-sulphur protein RNase L inhibitor functions in translation termination. EMBO Rep. 11 (2010) 214–219. CrossrefGoogle Scholar

  • [34] Banerjee, D., Lelandais, G., Shukla, S., Mukhopadhyay, G., Jacq, D., Devaux, F. and Prasad, R. Responses of pathogenic and nonpathogenic yeast species to steroids reveal the functioning and evolution of multidrug resistance transcriptional networks. Eucaryot. Cell. 7 (2008) 68–77. CrossrefGoogle Scholar

  • [35] Mahe, Y., Lemoine, Y. and Kuchler, K. The ATP-binding cassette transporters Pdr5 and Snq2 of Saccharomyces cerevisiae can mediate transport of steroids in vivo. J. Biol. Chem. 271 (1996) 25167–25172. Google Scholar

  • [36] Kihara, A. and Igarashi, Y. Cross talk between sphingolipids and glycerophospholipids in the establishment of plasma membrane asymmetry. Mol. Biol. Cell. 15 (2004) 4949–4959. CrossrefGoogle Scholar

  • [37] Hlavacek, O., Kucerova, H., Harant, K., Palkova, Z. and Vachova, L. Putative role for ABC multidrug exporters in yeast quorum sensing. FEBS Lett. 583 (2009) 1107–1113. Google Scholar

  • [38] Miyahara, K., Mizunuma, M., Hirata, D., Tsuchiya, E. and Miyakawa, T. The involvement of the Saccharomyces cerevisiae multidrug resistance transporters Pdr5 and Snq2 in cation resistance. FEBS Lett. 399 (1996) 317–320. Google Scholar

  • [39] Prunuske, A.J., Waltner, J.K., Kuhn, P., Gu, B. and Craig, E.A. Role of the molecular chaperones Zuo1 and Ssz1 in quorum sensing via activation of the transcription factor Pdr1. Proc. Natl. Acad. Sci. USA 109 (2012) 472–477. CrossrefGoogle Scholar

  • [40] Hellauer, K., Akache, B., MacPherson, S., Sirard, E. and Turcotte, B. Zinc cluster protein Rdr1p is a transcriptional repressor of the PDR5 gene encoding a multidrug transporter. J. Biol. Chem. 277 (2002) 17671–17676. Google Scholar

  • [41] Miyahara, K., Hirata, D. and Miyakawa, T. yAP-1 and yAP-2-mediated, heat shock-induced transcriptional activation of the multidrug resistance ABC transporter genes in Saccharomyces cerevisiae. Curr. Genet. 29 (1996) 103–105. Google Scholar

  • [42] Servos, J., Haase, E. and Brendel, M. Gene SNQ2 of Saccharomyces cerevisiae, which confers resistance to 4-nitroquinoline-N-oxide and other chemicals, encodes a 169 kDa protein homologous to ATP-dependent permeases. Mol. Gen. Genet. 236 (1993) 214–218. Google Scholar

  • [43] Akache, B. and Turcotte, B. New regulators of drug sensitivity in the family of yeast zinc cluster proteins. J. Biol. Chem. 277 (2002) 21254–21260. Google Scholar

  • [44] Larochelle, M., Drouin, S., Robert, F. and Turcotte, B. Oxidative stressactivated zinc cluster protein Stb5 has dual activator/repressor functions required for pentose phosphate pathway regulation and NADPH production. Mol. Cell. Biol. 26 (2006) 6690–6701. Google Scholar

  • [45] Le Crom, S., Devaux, F., Marc, P., Zhang, X., Moye-Rowley, W.S. and Jacq, C. New insights into the pleiotropic drug resistance network from genome-wide characterization of the Yrr1 transcription factor regulation system. Mol. Cell. Biol. 22 (2002) 2642–2649. CrossrefGoogle Scholar

  • [46] Wolfger, H., Mahe, Y., Parle-McDermott, A., Delahodde, A. and Kuchler, K. The yeast ATP-binding cassette (ABC) protein genes PDR10 and PDR15 are novel targets for the Pdr1 and Pdr3 transcriptional regulators. FEBS Lett. 418 (1997) 269–274. Google Scholar

  • [47] Hikkel, I., Lucau-Danila, A., Delaveau, T., Marc, P., Devaux, F. and Jacq, C. A general strategy to uncover transcription factor properties identifies a new regulator of drug resistance in yeast. J. Biol. Chem. 278 (2003) 11427–11432. CrossrefGoogle Scholar

  • [48] Wolfger, H., Mamnun, Y.M. and Kuchler, K. The yeast Pdr15p ATPbinding cassette (ABC) protein is a general stress response factor implicated in cellular detoxification. J. Biol. Chem. 279 (2004) 11593–11599. Google Scholar

  • [49] Rockwell, N.C., Wolfger, H., Kuchler, K. and Thorner, J. ABC transporter Pdr10 regulates the membrane microenvironment of Pdr12 in Saccharomyces cerevisiae. J. Membr. Biol. 229 (2009) 27–52. Google Scholar

  • [50] Hatzixanthis, K., Mollapour, M., Seymour, I., Bauer, B.E., Krapf, G., Schuller, C., Kuchler, K. and Piper, P.W. Moderately lipophilic carboxylate compounds are the selective inducers of the Saccharomyces cerevisiae Pdr12p ATP-binding cassette transporter. Yeast 20 (2003) 575–585. Google Scholar

  • [51] Gregori, C., Schuller, C., Frohner, I.E., Ammerer, G. and Kuchler, K. Weak organic acids trigger conformational changes of the yeast transcription factor War1 in vivo to elicit stress adaptation. J. Biol. Chem. 283 (2008) 25752–25764. Google Scholar

  • [52] Kren, A., Mamnun, Y.M., Bauer, B.E., Schuller, C., Wolfger, H., Hatzixanthis, K., Mollapour, M., Gregori, C., Piper, P., and Kuchler, K. War1p, a novel transcription factor controlling weak acid stress response in yeast. Mol. Cell. Biol. 23 (2003) 1775–1785. CrossrefGoogle Scholar

  • [53] Marek, M., Milles, S., Schreiber, G., Daleke, D.L., Dittmar, G., Herrmann, A., Muller, P. and Pomorski, T.G. The yeast plasma membrane ATP-binding cassette (ABC) transporter Aus1: purification, characterization and the effect of lipids on its activity. J. Biol. Chem. 286 (2011) 21835–21843. Google Scholar

  • [54] Cabrito, T.R., Teixeira, M.C., Singht, A., Prasad, R. and Sa-Correia, I. The yeast ABC transporter Pdr18 (ORF YNR070w) controls plasma membrane sterol composition, playing a role in multidrug resistance. Biochem. J. 440 (2011) 195–202. Google Scholar

  • [55] Teixeira, M.C., Godinho, C.P., Cabrito, T.R., Mira, N.P. and Sa-Correia, I. Increased expression of the yeast multidrug resistance transporter Pdr18 leads to increased ethanol tolerance and ethanol production in high gravity alcoholic fermentation. Microb. Cell Fact. 11 (2012) 98. CrossrefGoogle Scholar

  • [56] Prasad, R. and Goffeau, A. Yeast ATP-binding cassette transporters conferring multidrug resistance. Annu. Rev. Microbiol. 66 (2012) 39–63. CrossrefGoogle Scholar

  • [57] Prasad, R., Murthy, S.K., Gupta, V. and Prasad, R. Multiple drug resistance in Candida albicans. Acta Biochim. Pol. 42 (1995) 497–594. Google Scholar

  • [58] Nakamura, K., Niimi, M., Niimi, K., Holmes, A.R., Yates, J.E., Decottignies, A., Monk, B.C., Goffeau, A. and Cannon, R.D. Functional expression of Candida albicans drug efflux pump Cdr1p in a Saccharomyces cerevisiae strain deficient in membrane transporters. Antimicrob. Agents Chemother. 45 (2001) 3366–3374. Google Scholar

  • [59] Cannon, R.D., Lamping, E., Holmes, A.R., Niimi, K., Baret, P.V., Keniya, M.V., Tanabe, K., Niimi, M., Goffeau, A. and Monk, B.C. Efflux-mediated antifungal drug resistance. Clin. Microbiol. Rev. 22 (2009) 291–321. CrossrefGoogle Scholar

  • [60] Sanglard, D., Ischer, F., Monod, M. and Bille, J. Cloning of Candida albicans genes conferring resistance to azole antifungal agents: characterization of CDR2, a new multidrug ABC transporter gene. Microbiology 143 (1997) 405–416. Google Scholar

  • [61] Posteraro, B., Sanguinetti, M., Sanglard, D., La Sorda, M., Boccia, S., Romano, L., Morace, G. and Fadda, G. Identidification and characterization of a Cryptococcus neoformans ATP binding cassette (ABC) transporterencoding gene, CnAFR1, involved in the resistance to fluconazole. Mol. Microbiol. 47 (2003) 357–371. CrossrefGoogle Scholar

  • [62] Tobin, M.B., Peery, R.B. and Skatrud, P.L. Genes encoding multiple drug resistance-like proteins in Aspergillus fumigatus and Aspergillus flavus. Gene 200 (1997) 11–23. Google Scholar

  • [63] Slaven, J.W., Anderson, M.J., Sanglard, D., Dixon, G.K., Bille, J., Roberts, I.S. and Denning, D.W. Increased expression of a novel Aspergillus fumigatus ABC transporter gene, atrF, in the presence of itraconazole in an itraconazole resistant clinical isolate. Fungal Genet. Biol. 36 (2002) 199–206. CrossrefGoogle Scholar

  • [64] Choi, C.H. ABC transporters as multidrug resistance mechanisms and the development of chemosensitizers for their reversal. Cancer Cell Int. 5 (2005) 30. CrossrefGoogle Scholar

  • [65] Al-Shawi, M.K. and Omote, H. The remarkable transport mechanism of P-glycoprotein; a multidrug transporter. J. Bioenerg. Biomembr. 6 (2005) 489–496. Google Scholar

  • [66] Ni, Z. and Mao, Q. ATP-binding cassette efflux transporters in human placenta. Curr. Pharm. Biotechnol. 12 (2011) 674–685. CrossrefGoogle Scholar

  • [67] Kolaczkowska, A. and Goffeau, A. Regulation of pleiotropic drug resistance in yeast. Drug Resist. Updat. 2 (1999) 403–414. Google Scholar

  • [68] Katzmann, D.J., Hallstrom, T.C., Mahe, Y. and Moye-Rowley, W.S. Multiple Pdr1p/Pdr3p binding sites are essential for normal expression of the ATP binding cassette transporter protein-encoding gene PDR5. J. Biol. Chem. 271 (1996) 23049–23054. Google Scholar

  • [69] Poch, O. Conservation of a putative inhibitory domain in the GAL4 family members. Gene 184 (1997) 229–235. Google Scholar

  • [70] Martens, J.A., Genereaux, J., Saleh, A. and Brandle, C.J. Transcriptional activation by yeast PDR1p is inhibited by its association with NGG1p/ADA3p. J. Biol. Chem. 271 (1996) 15884–15890. Google Scholar

  • [71] Carvajal, E., van den Hazel, H.B., Cybularz-Kołaczkowska, A., Balzi, E. and Goffeau, A. Molecular and phenotypic characterization of yeast PDR1 mutants that show hyperactive transcription of various ABC multidrug transporter genes. Mol. Gen. Genet. 256 (1997) 406–415. Google Scholar

  • [72] DeRisi, J., van den Hazel, H.B., Marc, P., Balzi, E., Brown, P., Jacq, C. and Goffeau, A. Genome microarray analysis of transcriptional activation in multidrug resistance yeast mutants. FEBS Lett. 470 (2000) 156–160. Google Scholar

  • [73] Rank, G.H., Gerlach, J.H. and Robertson, A.J. Some physiological alteration associated with pleiotropic cross resistance and collateral sensitivity in Saccharomyces cerevisiae. Mol. Gen. Genet. 144 (1976) 281–288. CrossrefGoogle Scholar

  • [74] Kean, L.S., Grant, A.M., Angeletti, C., Mahe, Y., Kuchler, K., Fuller, R.S. and Nichols, J.W. Plasma membrane translocation of fluorescent-labeled phosphatidylethanolamine is controlled by transcription regulators, PDR1 and PDR3. J. Cell Biol. 138 (1997) 255–270. Google Scholar

  • [75] Hallstrom, T.C., Lambert, L., Schorling, S., Balzi, E., Goffeau, A. and Moye-Rowley, W.S. Coordinate control of sphingolipid biosynthesis and multidrug resistance in Saccharomyces cerevisiae. J. Biol. Chem. 276 (2001) 23674–23680. Google Scholar

  • [76] Decottignies, A., Grants, A.M., Nichols, J.W., de Wet, H., McIntosh, D.B. and Goffeau, A. ATPase and multidrug transport activities of the overexpressed yeast ABC protein Yor1p. J. Biol. Chem. 273 (1998) 12612–12622. Google Scholar

  • [77] Kralli, A., Bohen, S.P. and Yamamoto, K.R. LEM1, an ATP-bindingcassette transporter, selectively modulates the biological potency of steroid hormones. Proc. Natl. Acad. Sci. USA 92 (1995) 4701–4705. CrossrefGoogle Scholar

  • [78] Nourani, A., Wesolowski-Louvel, M., Delaveau, T., Jacq, C. and Delahodde, A. Multiple-drug-resistance phenomenon in the yeast Saccharomyces cerevisiae: involvement of two hexose transporters. Mol. Cell. Biol. 17 (1997) 5453–5460. Google Scholar

  • [79] do Valle Mata, M.A., Jonniaux, J.-L., Balzi, E., Goffeau, A. and van den Hazel, B. Novel target genes of the yeast regulator Pdr1p: a contribution of the TPO1 gene in resistance to quinidine and other drugs. Gene 272 (2001) 111–119. Google Scholar

  • [80] Delaveau, T., Delahodde, A., Carvajal, E., Subik, J. and Jacq, C. PDR3, a new yeast regulatory gene, is homologous to PDR1 and controls multidrug resistance phenomenon. Mol. Gen. Genet. 244 (1994) 501–511. Google Scholar

  • [81] Cui, Z., Shiraki, T., Hirata, D. and Miyakawa, T. Yeast gene YRR1, which is required for resistance to 4-nitroquinoline N-oxide, mediates transcriptional activation of the multidrug resistance transporter gene SNQ2. Mol. Microbiol. 29 (1998) 1307–1315. CrossrefGoogle Scholar

  • [82] Schmitt, A.P. and McEntee, K. Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. USA 93 (1996) 5777–5782. CrossrefGoogle Scholar

  • [83] Delahodde, A., Delaveau, T. and Jacq, C. Positive autoregulation of the yeast transcription factor Pdr3p, which is involved in control of drug resistance. Mol. Cell Biol. 15 (1995) 4043–4051. Google Scholar

  • [84] Hallstrom, T.C., Katzmann, D. J., Torres, R.J., Sharp, W.J. and Moye-Rowley, W.S. Regulation of transcription factor Pdr1 function by Hsp70 protein in Saccharomyces cereviasiae. Mol. Cell. Biol. 18 (1998) 1147–1155. Google Scholar

  • [85] Hahn, J.-S., Neef, D.W. and Thiele, D.J. A stress regulatory network for coordinated activation of proteasome expression mediated by yeast heat shock transcription factor. Mol. Microbiol. 60 (2006) 240–251. CrossrefGoogle Scholar

  • [86] Wendler, F., Bergler, H., Prutej, K., Jungwirth, H., Zisser, G., Kuchler, K. and Hogenauer, G. Diazaborine resistance in the yeast Saccharomyces cerevisiae reveals a link between YAP1 and the pleiotropic drug resistance genes PDR1 and PDR3. J. Biol. Chem. 272 (1997) 27091–27098. Google Scholar

  • [87] Bartosiewicz, D. and Krasowska, A. Inhibitors of ABC transporters and biophysical methods to study their activity. Z. Naturforsch. 64 (2009) 454–458. Google Scholar

  • [88] Ozben, T. Mechanisms and strategies to overcome multiple drug resistance. FEBS Lett. 580 (2006) 2903–2909. Google Scholar

  • [89] Chen, T. Overcoming drug resistance by regulating nuclear receptors. Adv. Drug Deliv. Rev. 62 (2010) 1257–1264. CrossrefGoogle Scholar

  • [90] Miller, T.P., Grogan, T.M., Dalton, W.S., Spier, C.M., Scheper, R.J. and Salmon, S.E. P-glycoprotein expression in malignant lymphoma and reversal of clinical drug resistance with chemotherapy plus high dose verapamil. J. Clin. Oncol. 9 (1991) 17–24. Google Scholar

  • [91] de Souza, P.S., Vasconcelos, F.C., Silva, L.F.R. and Maia R.C. Cyclosporin A enables vincristine-induced apoptosis during reversal of multidrug resistance phenotype in chronic myeloid leukemia cells. Tumor Biol. 33 (2012) 943–956. CrossrefGoogle Scholar

  • [92] Bankstahl, J.P., Kuntner, C., Abrahim, A., Karch, R., Stanek, J., Wanek, T., Wadsak, W., Kletter, K., Muller, M., Loscher, W. and Langer, O. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET. J. Nucl. Med. 49 (2008) 1328–1335. CrossrefGoogle Scholar

  • [93] Gadhe, C.G., Madhavan, T., Kothandan, G. and Cho, S.J. In silico quantitative structure-activity relationship studies on P-gp modulators of tetrahydroisoquinoline-ethyl-phenylamine series. BMC Struc. Biol. 11 (2011) 5. Google Scholar

  • [94] Martin, C., Berridge, G., Mistry, P., Higgins, C., Charlton, P. and Callaghan, R. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein. Br. J. Pharmacol. 128 (1999) 403–411. Google Scholar

  • [95] Gandhi, L., Harding, M.W., Neubauer, M., Langer, C.J., Moore, M., Ross, H.J., Johnson, B.E. and Lynch, T.J. A phase II study of the safety and efficacy of the multidrug resistance inhibitor VX-710 combined with doxorubicin and vincristine in patients with recurrent small cell lung cancer. Cancer 109 (2007) 924–932. CrossrefGoogle Scholar

  • [96] Molnar, J., Gyemant, N., Mucsi, I., Molnar, A., Szabo, M., Kortvelyesi, T., Varga, A., Molnar, P. and Toth, G. Modulation of multidrug resistance and apoptosis of cancer cells by selected carotenoids. In Vivo 18 (2004) 237–244. Google Scholar

  • [97] Gyemant, N., Tanaka, M., Molnar, P., Deli, J., Mandoky, L. and Molnar, J. Reversal of multidrug resistance of cancer cells in vitro: modification of drug resistance by selected carotenoids. Anticancer Res. 26 (2006) 367–374. Google Scholar

  • [98] Gyemant, N., Tanaka, M., Antus, S., Hohmann, J., Csuka, O., Mandoky, L. and Molnar, J. In vitro search for synergy between flavonoids and epirubicin on multidrug-resistant cancer cells. In Vivo 19 (2005) 367–374. Google Scholar

  • [99] Zhu, L., Zhao, L., Wang, H., Wang, Y., Pan, D., Yao, J., Li, Z., Wu, G. and Guo, Q. Oroxylin A reverses P-glycoprotein-mediated multidrug resistance of MCF7/ADR cells by G2/M arrest. Toxicol. Lett. 219 (2013) 107–115. Google Scholar

  • [100] Cheng, J., Cheng, L., Chen, B., Xia, G., Gao, C., Song, H., Bao, W., Guo, Q., Zhang, H. and Wang, X. Effect of magnetic nanoparticles of Fe3O4 and wogonin on the reversal of multidrug resistance in K562/A02 cell line. Int. J. Nanomedicine 7 (2012) 2843–2852. Google Scholar

  • [101] Bois, F., Boumendjel, A., Mariotte, A.M., Conseil, G. and Di Petro, A. Synthesis and biological activity of 4-alkyloxy chalcones: potential hydrophobic modulators of P- glycoprotein-mediated multidrug resistance. Bioorg. Med. Chem. 7 (1999) 2691–2695. CrossrefGoogle Scholar

  • [102] Liu, X.L., Tee, H.W and Go, M.L. Functionalized chalcones as selective inhibitors of P-glycoprotein and breast cancer resistance protein. Bioorg. Med. Chem. 16 (2008) 171–180. CrossrefGoogle Scholar

  • [103] Bulatova, N.R. and Darwish, R.M. Effect of chemosensitizers on minimum inhibitory concentrations of fluconazole in Candida albicans. Med. Princ. Pract. 17 (2008) 117–121. CrossrefGoogle Scholar

  • [104] Maesaki, S., Marichal, P., Hossain, M.A., Sanglard, D., Vanden Bossche, H. and Kohno, S. Synergic effects of tacrolimus and azole antifungal agents against azole-resistant Candida albicans strains. J. Antimicrob. Chemother. 42 (1998) 747–753. CrossrefGoogle Scholar

  • [105] Lamoureux, F., Mestre, E., Essig, M., Sauvage, F.L., Marquet, P. and Gastinel, L.N. Quantitative proteomic analysis of cyclosporine-induced toxicity in human kidney cell line andcomparison with tacrolimus. J. Proteomics 75 (2011) 677–694. CrossrefGoogle Scholar

  • [106] Roberts, C.A., Stern, D.L. and Radio, S.J. Asymmetric cardiac hypertrophy at autopsy in patients who received FK506 (tacrolimus) or cyclosporine A after liver transplant. Transplantation 74 (2002) 817–821. Google Scholar

  • [107] Zhang, H., Gao, A., Li, F., Zhang, G., Ho, H.I. and Liao, W. Mechanism of action of tetrandrine, a natural inhibitor of Candida albicans drug efflux pumps. Yakugaku Zasshi 129 (2009) 623–630. CrossrefGoogle Scholar

  • [108] Ricardo, E., Costa-de-Oliveira, S., Dias, A.S., Guerra, J., Rodrigues, A.G. and Pina-Vaz, C. Ibuprofen reverts antifungal resistance on Candida albicans showing overexpression of CDR genes. FEMS Yeast Res. 9 (2009) 618–625. CrossrefGoogle Scholar

  • [109] Schuetzer-Muehlbauer, M., Willinger, B., Egner, R., Ecker, G. and Kuchler, K. Reversal of antifungal resistance mediated by ABC efflux pumps from Candida albicans functionally expressed in yeast. Int. J. Antimicrob. Agents 22 (2003) 291–300. CrossrefGoogle Scholar

  • [110] Shukla, S., Sauna, Z.E., Prasad, R. and Ambudkar, S.V. Disulfiram is a potent modulator of multidrug transporter Cdr1p of Candida albicans. Biochem. Biophys. Res. Commun. 322 (2004) 520–525. Google Scholar

  • [111] Conseil, G., Perez-Victoria, J.M., Renoir, J.M., Goffeau, A. and Di Pietro, A. Potent competitive inhibition of drug binding to the Saccharomyces cerevisiae ABC exporter Pdr5p by the hydrophobic estradiol-derivative RU49953. Biochim. Biophys. Acta 1614 (2003) 131–134. Google Scholar

  • [112] Banerjee, D., Lelandais, G, Shukla, S., Mukhopadhyay, G., Jacq, C., Devaux, F. and Prasad, R. Responses of pathogenic and nonpathogenic yeast species to steroids reveal the functioning and evolution of multidrug resistance transcriptional networks. Eucaryot. Cell 7 (2008) 68–77. CrossrefGoogle Scholar

  • [113] Kołaczkowski, M., van der Rest, M., Cybularz-Kołaczkowska, A., Soumillion, J.P., Konings, W.N. and Goffeau, A. Anticancer drugs, ionophoric peptides, and steroids as substrates of the yeast multidrug transporter Pdr5p. J. Biol. Chem. 271 (1996) 31543–31548. Google Scholar

  • [114] Kołaczkowski, M., Michalak, K., and Motohashi, N. Phenotiazines as potent modulators of yeast multidrug resistance. Int. J. Antimicrob. Agents 22 (2003) 279–283. CrossrefGoogle Scholar

  • [115] Conseil, G., Decottignies, A., Jault, J.M., Comte, G., Barron, D., Goffeau, A. and Di Pietro, A. Prenyl-flavonoids as potent inhibitors of the Pdr5p multidrug ABC transporter from Saccharomyces cerevisiae. Biochemistry 39 (2000) 6910–6917. CrossrefGoogle Scholar

  • [116] Wesołowska, O. Interaction of phenotiazines, stilbenes and flavonoids with multidrug resistance-associated transporters, P-glycoprotein and MRP1. Acta Biochim. Pol. 58 (2011) 433–448. Google Scholar

  • [117] Rosso, J., Zachowski, A. and Devaux, P.F. Influence of chlorpromazine on the transverse mobility of phospholipids in the human erythrocyte membrane: relation to shape changes. Biochim. Biophys. Acta 942 (1988) 271–279. Google Scholar

  • [118] Kolaczkowski, M., Kolaczkowska, A., Motohashi, N. and Michalak, K. New high-throughput screening assay to reveal similarities and differences in inhibitory sensitivities of multidrug ATP-binding cassette transporters. Antimicrob. Agents Chemother. 53 (2009) 1516–1527. Google Scholar

  • [119] Kaatz, G.W., Moudgal, V.V., Seo, S.M. and Kristiansen, J.E. Phenothiazines and thioxanthenes inhibit multidrug efflux pump activity in Staphylococcus aureus. Antimicrob. Agents. Chemother. 47 (2003) 719–726. CrossrefGoogle Scholar

  • [120] Safa, A.R. Photoaffinity labels for characterizing drug interaction sites of P-glycoprotein. Methods Enzymol. 292 (1998) 289–307. Google Scholar

  • [121] Hiraga, K., Yamamoto, S., Fukuda, H., Hamanaka, N. and Oda, K. Enniatin has a new function as an inhibitor of Pdr5p, one of the ABC transporters in Saccharomyces cerevisiae. Biochem. Biophys. Res. Commun. 328 (2005) 1119–1125. Google Scholar

  • [122] Niimi, K., Harding, D.R.K., Parshot, R., King, A., Lun, D.J., Decottignies, A., Niimi, M., Lin, S., Cannon, R.D., Goffeau, A. and Monk, B.C. Chemosensitization of fluconazol resistance in Saccharomyces cerevisiae and pathogenic fungi by a D-octapeptide derivative. Antimicrob. Agents Chemother. 48 (2004) 1256–1271. Google Scholar

  • [123] Cernicka, J., Kozovska, Z., Hnatova, M., Valachovic, M., Hapala, I., Riedl, Z., Hajos, G. and Subik, J. Chemosensitization of drug-resistant and drugsensitive yeast cells to antifungals. Int. J. Antimicrob. Agents 29 (2007) 170–178. CrossrefGoogle Scholar

  • [124] Tanida, T., Okamoto, T., Ueta, E., Yamamoto, T. and Osaki, T. Antimicrobial peptides enhance the candidacidal activity of antifungal drugs by promoting the efflux of ATP from Candida cells. J. Antimicrob. Chemother. 57 (2006) 94–103. Google Scholar

About the article

Published Online: 2014-03-26

Published in Print: 2014-03-01

Citation Information: Cellular and Molecular Biology Letters, Volume 19, Issue 1, Pages 1–22, ISSN (Online) 1689-1392, DOI: https://doi.org/10.2478/s11658-013-0111-2.

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