TAILIEUCHUNG - Báo cáo khóa học: 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 cerevisiaethis pheno-menon 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 PDR1-12and PDR3-33,respectively, mediate resistance to diazaborine | Eur. J. Biochem. 271 1145-1152 2004 FEBS 2004 doi The transporters Pdr5p and Snq2p mediate diazaborine resistance and are under the control of the gain-of-function allele PDR1-12 Eva Wehrschutz-Sigl Helmut Jungwirth Helmut Bergler and Gregor Hogenauer Institut fur Molekularbiologie Biochemie und Mikrobiologie Karl-Franzens-Universitat Graz Austria 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 retistance to diazaborine. Here we demonstrate that the transporters Pdrlp and Snq2p are involved in diazaborine detoxification. We report that in the PDR3-33 mutant diazaborine resistanev is exerted mainly via overexpression of the PDR5 and SNQ2 genes while in the PDR1-12 mutant odditignal vgneel tile Yap p target genes FLR1 and YCF1 are abo mvolvdl m diazaborine detoxification. In addition we tCow th Ú1 the presenev of cycloheximide or diazaborine PDR5 can be activated by additional transcription factors beside Pdr p and Pdr3p. Keywords diazaborine ABC transporters transcriptional regulation Saccharomyces cerevisiae. Yeast Saccharomyces cerevisiae is equipped with a detoxification mechanism called the pleiotropic drug resistance PDR network will ch pHUc the elll í rom a numbr of structurally and functionally unrelated toxic compounds 1 2 . The PDR-system involves complex interactions between a set of regulatory proteins and membrane-located efflux pumps from the ATP-binding-cassette ABC or the major facilitator superfamily MFS type which eliminate toxic compounds from the cell 1 3 . The master regulators of the

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