Compensatory activation of the multidrug transporters Pdr5p, Snq2p, and Yor1p by Pdr1p in Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, the transcription factors Pdr1p and Pdr3p activate the expression of several genes, including PDR5, SNQ2, and YOR1, which encode ATP-binding cassette transporters that extrude dozens of antifungals with overlapping but distinct specificity. In this study, it was observed that growth resistance to specific Pdr5p substrates rose upon disruption of the YOR1 or SNQ2 coding region and was accompanied by increased efflux. Similarly, resistance to Yor1p- and Snq2p-specific substrates increased upon deletion of PDR5. The mRNA and protein levels of the respective transporters increased in parallel to drug resistance. beta-Galactosidase activity fused to the PDR5 or YOR1 promoter required the presence of Pdr1p and its specific binding sites for the compensatory induction, whereas Pdr3p had an inhibitory effect.
Kolaczkowska
Anna
A
Faculty of Biotechnology, University of Wroclaw, ul. Tamka 2, 50-137 Wroclaw, Poland. anikolo1@poczta.onet.pl <anikolo1@poczta.onet.pl>
Kolaczkowski
Marcin
M
Goffeau
André
A
Moye-Rowley
W Scott
WS
D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology; D001393:Azoles / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D026141:Drug Resistance, Multiple, Fungal / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D017930:Genes, Reporter; D008928:Mitochondria / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D001616:beta-Galactosidase / Q000235:genetics
D018528:ATP-Binding Cassette Transporters; D000935:Antifungal Agents; D001393:Azoles; D004268:DNA-Binding Proteins; C085480:PDR1 protein, S cerevisiae; C089261:PDR3 protein, S cerevisiae; C092438:PDR5 protein, S cerevisiae; D012333:RNA, Messenger; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C097077:YOR1 protein, S cerevisiae; D001616:beta-Galactosidase