The transporters Pdr5p and Snq2p mediate diazaborine resistance and are under the control of the gain-of-function allele PDR1-12.
The spontaneous acquisition of resistance to a variety of unrelated cytotoxic compounds has important implications in medical treatment of infectious diseases and anticancer therapy. In the yeast Saccharomyces cerevisiae this phenomenon is caused by overexpression of membrane efflux pumps and is called pleiotropic drug resistance. We have found that allelic forms of the genes for the transcription activators Pdr1p and Pdr3p, designated PDR1-12 and PDR3-33, respectively, mediate resistance to diazaborine. Here we demonstrate that the transporters Pdr5p and Snq2p are involved in diazaborine detoxification. We report that in the PDR3-33 mutant diazaborine resistance is exerted mainly via overexpression of the PDR5 and SNQ2 genes, while in the PDR1-12 mutant, additional genes, i.e. the Yap1p target genes FLR1 and YCF1, are also involved in diazaborine detoxification. In addition, we show that in the presence of cycloheximide or diazaborine PDR5 can be activated by additional transcription factors beside Pdr1p and Pdr3p.
Institut für Molekularbiologie, Biochemie und Mikrobiologie, Karl-Franzens-Universität Graz, Austria.
Eva
E
Wehrschütz-Sigl
Helmut
H
Jungwirth
Helmut
H
Bergler
Gregor
G
Högenauer
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000483:Alleles; D001372:Aza Compounds / Q000378:metabolism / Q000494:pharmacology*; D015152:Blotting, Northern; D001896:Boron Compounds / Q000378:metabolism / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004351:Drug Resistance; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; D012333:RNA, Messenger / Q000096:biosynthesis; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D018528:ATP-Binding Cassette Transporters; D048868:Adaptor Proteins, Signal Transducing; D001372:Aza Compounds; D001896:Boron Compounds; D002352:Carrier Proteins; C118429:FLR1 protein, S cerevisiae; D026901:Membrane Transport Proteins; D027361:Organic Anion Transporters; C092438:PDR5 protein, S cerevisiae; C472673:Pdr12 protein, S cerevisiae; D012333:RNA, Messenger; C101797:SNQ2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C477161:YBP1 protein, S cerevisiae; C089179:YCF1 protein, S cerevisiae; D003513:Cycloheximide