The ATP‐binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3
Abstract
Summary: Pleiotropic drug resistance (PDR) in the yeast Saccharomyces cerevisiae can arise from overexpression of ATP‐binding cassette (ABC) efflux pumps such as Pdr5 and Snq2. Mutations in the transcription factor genes PDR1 and PDR3 are also associated with PDR. We show here that a pdr1–3 mutant exhibits a PDR phenotype, including elevated resistance to the mutagen 4‐nitroquinoline‐N‐oxide, a known substrate for Snq2 but not for Pdr5. Northern analysis and immunoblotting demonstrated that the SNQ2 gene is 10‐fold overexpressed in a pdr1–3 gain‐of‐function mutant strain, whereas Snq2 expression is severely reduced in a Δ pdr1 deletion strain, and almost abolished in a Δ pdr1 Δ pdr3 double disruptant when compared to the PDR1 strain. However, expression of the Ste6 a‐factor pheromone transporter, another yeast ABC transporter not associated with PDR, is unaffected in pdr1–3 mutant cells and in strains carrying Δ pdr1, Δ pdr3, or Δ pdr1 Δ pdr3 deletions. Finally, DNA footprint analysis revealed that the SNQ2 promoter contains three binding sites for Pdr3. Our results identify SNQ2 as a novel target for both Pdr1 and Pdr3, and demonstrate that the PDR phenotype of a pdr1–3 mutant strain results from overexpression of more than one ABC drug‐efflux pump.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Expression of PDR5 and the other PDR network genes in S. cerevisiae is regulated by Pdr1 and Pdr3, key transcription factors whose functions are partially redundant.
“The expression of PDR5 and the other PDR network genes in S. cerevisiae is regulated by Pdr1 and Pdr3, key transcription factors whose functions are partially redundant10–12.”
From SWI/SNF and the histone chaperone Rtt106 drive expression of the Pleiotropic Drug Resistance network genes (2022) · cites this paper as [12]
Cites
Molecular cloning: A laboratory manual
Deininger, P. L. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90595-z · Cited by 84,684 · see citing works
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.76.9.4350 · Cited by 51,421 · see citing works
Antibodies, a laboratory manual
(1989) · Biomedicine & Pharmacotherapy · doi:10.1016/0753-3322(89)90130-3 · Cited by 12,318 · see citing works
Current protocols in molecular biology
Dudley, R. K. (1988) · FEBS Letters · doi:10.1016/0014-5793(88)80264-3 · Cited by 6,004 · see citing works
ABC Transporters: From Microorganisms to Man
Higgins, C. F. (1992) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.08.110192.000435 · Cited by 3,985 · see citing works
Overexpression of a Transporter Gene in a Multidrug-Resistant Human Lung Cancer Cell Line
Cole, S. P. C., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M. V., & Deeley, R. G. (1992) · Science · doi:10.1126/science.1360704 · Cited by 3,037 · see citing works
[10] 5-Fluoroorotic acid as a selective agent in yeast molecular genetics
Boeke, J. D., Trueheart, J., Natsoulis, G., & Fink, G. R. (1987) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(87)54076-9 · Cited by 1,368 · see citing works
A rapid and simple method for preparation of RNA from Saccharomyces cerevisiae
Schmitt, M. E., Brown, T. A., & Trumpower, B. L. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.10.3091 · Cited by 1,344 · see citing works
Targeting, disruption, replacement, and allele rescue: integrative DNA transformation in yeast.
Rothstein, R. (1991) · Methods in Enzymology · doi:10.1016/0076-6879(91)94022-5 · Cited by 1,283 · see citing works
Methods in Yeast Genetics — A Laboratory Course Manual
Radford, A. D. (1991) · Biochemical Education · doi:10.1016/0307-4412(91)90039-b · Cited by 1,258 · see citing works
Cell Biology: a Laboratory Handbook
Harris, A. (1995) · Journal of Medical Genetics · doi:10.1136/jmg.32.9.759 · Cited by 1,230 · see citing works
Alani, E., Cao, L., & Kleckner, N. E. (1987) · Genetics · doi:10.1534/genetics.112.541.test · Cited by 878 · see citing works
Sanglard, D., Kuchler, K., Ischer, F., Pagani, J. L., Monod, M., & Bille, J. (1995) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.39.11.2378 · Cited by 815 · see citing works
Self-citationThe human multidrug resistance-associated protein MRP is a plasma membrane drug-efflux pump.
Zaman, G. J., Flens, M. J., van Leusden, M. R., de Haas, M., MÜLDER, H. S., Lankelma, J., Pinedo, H. M., Scheper, R. J., Baas, F., & Broxterman, H. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.19.8822 · Cited by 679 · see citing works
The yeast STE6 gene encodes a homologue of the mammalian multidrug resistance P-glycoprotein
McGrath, J. P., & Varshavsky, A. J. (1989) · Nature · doi:10.1038/340400a0 · Cited by 590 · see citing works
Balzi, E., Wang, M., Leterme, S., Van Dyck, L., & Goffeau, A. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)42155-7 · Cited by 447 · see citing works
Saccharomyces cerevisiae STE6 gene product: a novel pathway for protein export in eukaryotic cells.
Kuchler, K., Sterne, R. E., & Thorner, J. W. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb08580.x · Cited by 446 · see citing works
Self-citationAlani, E. A., Cao, L., & Kleckner, N. E. (1987) · Genetics · doi:10.1093/genetics/116.4.541 · Cited by 417 · see citing works
Gallwitz, D., & Sures, I. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.5.2546 · Cited by 407 · see citing works
Yeast YAP1 encodes a novel form of the jun family of transcriptional activator proteins.Preprint
Moye-Rowley, S., Harshman, K., & Parker, C. S. (1989) · Genes & Development · doi:10.1101/gad.3.3.283 · Cited by 333 · see citing works
Kölling, R., & Hollenberg, C. P. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06627.x · Cited by 320 · see citing works
The multidrug resistance gene PDR1 from Saccharomyces cerevisiae.
Balzi, E., Chen, W., Ułaszewski, S., Capieaux, E., & Goffeau, A. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45464-6 · Cited by 268 · see citing works
Cloning of Two Novel ABC Transporters Mapping on Human Chromosome 9
Luciani, M., Denizot, F., Savary, S., Mattéi, M., & Chimini, G. (1994) · Genomics · doi:10.1006/geno.1994.1237 · Cited by 267 · see citing works
Bissinger, P. H., & Kuchler, K. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41760-1 · Cited by 234 · see citing works
Self-citationDelaveau, T., Delahodde, A., Carvajal, E., Šubík, J., & Jacq, C. (1994) · Molecular and General Genetics MGG · doi:10.1007/bf00583901 · Cited by 217 · see citing works
Self-citationKatzmann, D. J., Hallstrom, T. C., Voet, M., Wysock, W., Golin, J. E., Volckaert, G., & Moye-Rowley, S. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.12.6875 · Cited by 217 · see citing works
Transcriptional control of the yeast PDR5 gene by the PDR3 gene product.
Katzmann, D. J., Burnett, P. E., Golin, J. E., Mahé, Y., & Moye-Rowley, S. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.7.4653 · Cited by 216 · see citing works
Self-citationServos, J., Haase, E., & Brendel, M. (1993) · Molecular and General Genetics MGG · doi:10.1007/bf00277115 · Cited by 203 · see citing works
Cloning by gene amplification of two loci conferring multiple drug resistance in Saccharomyces.
Leppert, G. S., McDevitt, R. E., Falco, S. C., Dyk, T. K. V., Ficke, M. B., & Golin, J. E. (1990) · Genetics · doi:10.1093/genetics/125.1.13 · Cited by 183 · see citing works
(1990) · European Journal of Medicinal Chemistry · doi:10.1016/0223-5234(90)90153-t · Cited by 163 · see citing works
Decottignies, A., Lambert, L., Catty, P., Degand, H., Epping, E. A., Moye-Rowley, S., Balzi, E., & Goffeau, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.30.18150 · Cited by 162 · see citing works
Kralli, A., Bohen, S. P., & Yamamoto, K. R. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.10.4701 · Cited by 160 · see citing works
Interaction of the yeast pleiotropic drug resistance genes PDR1 and PDR5
Meyers, S., Schauer, W., Balzi, E., Wagner, M., Goffeau, A., & Golin, J. (1992) · Current Genetics · doi:10.1007/bf00351651 · Cited by 156 · see citing works
Genetics and biochemistry of yeast multidrug resistance
Balzi, E., & Goffeau, A. (1994) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/0005-2728(94)90102-3 · Cited by 152 · see citing works
Hirata, D., Yano, K., Miyahara, K., & Miyakawa, T. (1994) · Current Genetics · doi:10.1007/bf00310491 · Cited by 150 · see citing works
Delahodde, A., Delaveau, T., & Jacq, C. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4043 · Cited by 142 · see citing works
Self-citationEgner, R., Mahé, Y., Pandjaitan, R., & Kuchler, K. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.11.5879 · Cited by 127 · see citing works
Self-citationKuchler, K., Dohlman, H. G., & Thorner, J. W. (1993) · The Journal of Cell Biology · doi:10.1083/jcb.120.5.1203 · Cited by 99 · see citing works
Self-citationIdentification of tubulin from the yeast Saccharomyces cerevisiae.
Baum, P. R., Thorner, J. W., & Honig, L. S. (1978) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.75.10.4962 · Cited by 68 · see citing works
Use of polymerase chain reaction for rapid detection of gene insertions in whole yeast cells
Sathe, G. M., O'Brien, S., McLaughlin, M. M., Watson, F., & Livi, G. P. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.17.4775 · Cited by 56 · see citing works
Allikmets, R. L., Gerrard, B., Glavač, D., Ravnik‐Glavač, M., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Modi, W. S., & Dean, M. C. (1995) · Mammalian Genome · doi:10.1007/bf00303254 · Cited by 29 · see citing works
Kuchler, K., Goransson, H. M., Viswanathan, M. N., et al. (1992) · Cold Spring Harbor Symposia on Quantitative Biology · doi:10.1101/sqb.1992.057.01.064 · Cited by 22 · see citing works
Self-citationATP binding cassette transporters in yeast
Egner, R., Mahé, Y., Pandjaitan, R., Huter, V., Lamprecht, A., & Kuchler, K. (1995) · Membrane protein transport · doi:10.1016/s1874-592x(06)80004-1 · Cited by 17 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
A Fungal Family of Transcriptional Regulators: the Zinc Cluster Proteins
MacPherson, S., Larochelle, M., & Turcotte, B. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00015-06 · Cited by 612 · see citing works
Franz, R., Kelly, S. L., Lamb, D. C., Kelly, D. E., Ruhnke, M., & Morschhäuser, J. (1998) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.42.12.3065 · Cited by 339 · see citing works
Torelli, R., Posteraro, B., Ferrari, S., La Sorda, M., Fadda, G., Sanglard, D., & Sanguinetti, M. (2008) · Molecular Microbiology · doi:10.1111/j.1365-2958.2008.06143.x · Cited by 141 · see citing works
Multidrug resistance in fungi: regulation of transporter-encoding gene expression
Paul, S., & Moye-Rowley, W. S. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00143 · Cited by 137 · see citing works
Mamnun, Y. M., Pandjaitan, R., Mahé, Y., Delahodde, A., & Kuchler, K. (2002) · Molecular Microbiology · doi:10.1046/j.1365-2958.2002.03262.x · Cited by 125 · see citing works
Self-citationTalibi, D., & Raymond, M. (1999) · Journal of Bacteriology · doi:10.1128/jb.181.1.231-240.1999 · Cited by 101 · see citing works
Wolfger, H., Mahé, Y., Parle-McDermott, A., Delahodde, A., & Kuchler, K. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01382-3 · Cited by 97 · see citing works
Self-citationWirsching, S., Michel, S., Köhler, G., & Morschhäuser, J. (2000) · Journal of Bacteriology · doi:10.1128/jb.182.2.400-404.2000 · Cited by 88 · see citing works
Zhang, X., & Moye-Rowley, W. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106285200 · Cited by 84 · see citing works
Nikolov, V. N., Malavia, D., & Kubota, T. (2022) · Nature Communications · doi:10.1038/s41467-022-29591-z · Cited by 16 · see citing works
- Authors
- Mahé, Y., Parle‐McDermott, A., Nourani, A., Delahodde, A., Lamprecht, A., & Kuchler, K.
- Affiliations
- University of Vienna (AT)
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Kuchler, Karl
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 1996-04
- Volume
- 20
- Issue
- 1
- Pages
- 109-117
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2122882694
- Cited by
- 117
- References
- 43
- Citations by year
- 2025: 2 · 2024: 3 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 5 · 2016: 2 · 2014: 2 · 2013: 3
- FWCI
- 4.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- Oesterreichische Nationalbank
- Topics
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- ABC transporters, pleiotropic drug resistance, PDR1, PDR3, transcriptional regulation, PDR5, Saccharomyces cerevisiae, transcription factor binding sites
- MeSH terms
- Antifungal Agents, Binding Sites, Cycloheximide, DNA-Binding Proteins, Drug Resistance, Microbial, Fungal Proteins, Glycoproteins, Membrane Proteins, Mutagens, Mutation, Promoter Regions, Genetic, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Transcription Factors, 4-Nitroquinoline-1-oxide, Trans-Activators, Drug Resistance, Multiple, ATP-Binding Cassette Transporters, Saccharomyces cerevisiae Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review