Abstract
Multiple or pleiotropic drug resistance in the yeast Saccharomyces cerevisiae requires the expression of several ATP binding cassette transporter-encoding genes under the control of the zinc finger-containing transcription factor Pdrlp. The ATP binding cassette transporter-encoding genes regulated by Pdrlp include PDR5 and YOR1, which are required for normal cycloheximide and oligomycin tolerances, respectively. We have isolated a new member of the PDR gene family that encodes a member of the Hsp70 family of proteins found in this organism. This gene has been designated PDR13 and is required for normal growth. Overexpression of Pdr13p leads to an increase in both the expression of PDR5 and YOR1 and a corresponding enhancement in drug resistance. Pdr13p requires the presence of both the PDR1 structural gene and the Pdr1p binding sites in target promoters to mediate its effect on drug resistance and gene expression. A dominant, gain-of-function mutant allele of PDR13 was isolated and shown to have the same phenotypic effects as when the gene is present on a 2microm plasmid. Genetic and Western blotting experiments indicated that Pdr13p exerts its effect on Pdr1p at a posttranslational step. These data support the view that Pdr13p influences pleiotropic drug resistance by enhancing the function of the transcriptional regulatory protein Pdr1p.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ATP-Binding Cassette Transporters / biosynthesis
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ATP-Binding Cassette Transporters / genetics
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Animals
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Cycloheximide / pharmacology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Drug Resistance, Microbial / genetics
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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Gene Deletion
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Gene Dosage
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Gene Expression
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Genes, Fungal
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism*
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Membrane Proteins / biosynthesis
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Membrane Proteins / genetics
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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Protein Processing, Post-Translational
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / genetics
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae / metabolism*
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Saccharomyces cerevisiae Proteins*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / metabolism
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Zinc Fingers* / genetics
Substances
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ATP-Binding Cassette Transporters
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DNA-Binding Proteins
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Fungal Proteins
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HSP70 Heat-Shock Proteins
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Membrane Proteins
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Molecular Chaperones
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PDR1 protein, S cerevisiae
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PDR3 protein, S cerevisiae
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PDR5 protein, S cerevisiae
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Recombinant Fusion Proteins
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SSZ1 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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YOR1 protein, S cerevisiae
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Cycloheximide