Abstract
Screening for suppressors of canthin-6-one toxicity in yeast identified Yap1, a transcription factor involved in cell response to a broad range of injuries. Although canthin-6-one did not promote a significant oxidative stress, overexpression of YAP1 gene clearly increased resistance to this drug. We demonstrated that Yap1-mediated resistance involves the plasma membrane major-facilitator-superfamily efflux pump Flr1 but not the vacuolar ATP-binding-cassette transporter Ycf1. FLR1 overexpression was sufficient to reduce sensitivity to the drug, but strictly dependent on a functional YAP1 gene.
Keywords:
Canthin-6-one resistance; Membrane efflux pump; Saccharomyces cerevisiae; Transcription factor.
Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP-Binding Cassette Transporters / genetics
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ATP-Binding Cassette Transporters / metabolism
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Carbolines / pharmacology*
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Cell Membrane / drug effects
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Drug Resistance, Fungal / drug effects*
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Drug Resistance, Fungal / genetics
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Fungicides, Industrial / pharmacology*
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Gene Expression Regulation, Fungal / drug effects*
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Indole Alkaloids / pharmacology*
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Organic Anion Transporters / genetics*
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Organic Anion Transporters / metabolism
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Saccharomyces cerevisiae / drug effects*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / genetics*
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Saccharomyces cerevisiae Proteins / metabolism
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Signal Transduction
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Transcription Factors / genetics*
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Transcription Factors / metabolism
Substances
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ATP-Binding Cassette Transporters
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Carbolines
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FLR1 protein, S cerevisiae
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Fungicides, Industrial
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Indole Alkaloids
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Organic Anion Transporters
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Saccharomyces cerevisiae Proteins
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Transcription Factors
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YAP1 protein, S cerevisiae
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YCF1 protein, S cerevisiae
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canthin-6-one