Cited by 117Drug Transport and Resistance MechanismsFungal and yeast genetics researchBacterial Genetics and Biotechnology

The ATP‐binding cassette multidrug transporter Snq2 of Saccharomyces cerevisiae: a novel target for the transcription factors Pdr1 and Pdr3

Mahé, Yannick, Parle‐McDermott, Anne, Nourani, Amine, Delahodde, Agnès, Lamprecht, Andrea, Kuchler, Karl·1996·Molecular Microbiology

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.

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Crossref · 10.1111/j.1365-2958.1996.tb02493.x

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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

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