Multiple Yap1p-binding Sites Mediate Induction of the Yeast Major Facilitator FLR1 Gene in Response to Drugs, Oxidants, and Alkylating Agents

The bZip transcription factor Yap1p plays an important role in oxidative stress response and multidrug resistance in Saccharomyces cerevisiae. We have previously demonstrated that the FLR1 gene, encoding a multidrug transporter of the major facilitator superfamily, is a transcriptional target of Yap1p. The FLR1 promoter contains three potential Yap1p response elements (YREs) at positions −148 (YRE1), −167 (YRE2), and −364 (YRE3). To address the function of these YREs, the three sites have been individually mutated and tested in transactivation assays. Our results show that (i) each of the three YREs is functional and important for the optimal transactivation of FLR1 by Yap1p and that (ii) the three YREs are not functionally equivalent, mutation of YRE3 being the most deleterious, followed by YRE2 and YRE1. Simultaneous mutation of the three YREs abolished transactivation of the promoter by Yap1p, demonstrating that the three sites are essential for the regulation of FLR1 by Yap1p. Gel retardation assays confirmed that Yap1p differentially binds to the three YREs (YRE3 > YRE2 > YRE1). We show that the transcription of FLR1 is induced upon cell treatment with the oxidizing agents diamide, diethylmaleate, hydrogen peroxide, and tert-butyl hydroperoxide, the antimitotic drug benomyl, and the alkylating agent methylmethane sulfonate and that this induction is mediated by Yap1p through the three YREs. Finally, we show that FLR1 overexpression confers resistance to diamide, diethylmaleate, and menadione but hypersensitivity to H2O2, demonstrating that the Flr1p transporter participates in Yap1p-mediated oxidative stress response in S. cerevisiae. The bZip transcription factor Yap1p plays an important role in oxidative stress response and multidrug resistance in Saccharomyces cerevisiae. We have previously demonstrated that the FLR1 gene, encoding a multidrug transporter of the major facilitator superfamily, is a transcriptional target of Yap1p. The FLR1 promoter contains three potential Yap1p response elements (YREs) at positions −148 (YRE1), −167 (YRE2), and −364 (YRE3). To address the function of these YREs, the three sites have been individually mutated and tested in transactivation assays. Our results show that (i) each of the three YREs is functional and important for the optimal transactivation of FLR1 by Yap1p and that (ii) the three YREs are not functionally equivalent, mutation of YRE3 being the most deleterious, followed by YRE2 and YRE1. Simultaneous mutation of the three YREs abolished transactivation of the promoter by Yap1p, demonstrating that the three sites are essential for the regulation of FLR1 by Yap1p. Gel retardation assays confirmed that Yap1p differentially binds to the three YREs (YRE3 > YRE2 > YRE1). We show that the transcription of FLR1 is induced upon cell treatment with the oxidizing agents diamide, diethylmaleate, hydrogen peroxide, and tert-butyl hydroperoxide, the antimitotic drug benomyl, and the alkylating agent methylmethane sulfonate and that this induction is mediated by Yap1p through the three YREs. Finally, we show that FLR1 overexpression confers resistance to diamide, diethylmaleate, and menadione but hypersensitivity to H2O2, demonstrating that the Flr1p transporter participates in Yap1p-mediated oxidative stress response in S. cerevisiae. multidrug resistance benomyl cysteine-rich domain diamide diethylmaleate electrophoretic mobility shift assay fluconazole resistance 1 methylmethane sulfonate menadione open reading frame polymerase chain reaction tert-butyl hydroperoxide Yap1p response element synthetic dextrose wild type glyceraldehyde-3-phosphate dehydrogenase The Saccharomyces cerevisiae transcription factor Yap1p plays an important role in oxidative stress response and multidrug resistance (MDR)1 by activating target genes involved in cellular detoxification (1Bauer B.E. Wolfger H. Kuchler K. Biochim. Biophys. Acta. 1999; 1461: 217-236Crossref PubMed Scopus (228) Google Scholar, 2Toone W.M. Jones N. Curr. Opin. Genet. Dev. 1999; 9: 55-61Crossref PubMed Scopus (100) Google Scholar, 3Kolaczkowska A. Goffeau A. Drug Resist Update. 1999; 2: 403-414Crossref PubMed Scopus (106) Google Scholar). Yap1p belongs to the bZip (basic domain/leucine zipper) family of transcription factors that includes the yeast Gcn4p and the mammalian activator protein-1 proteins Fos and Jun (4Moye-Rowley W.S. Harshman K.D. Dev. PubMed Scopus Google Scholar). transcription by to in the promoter of W.M. Jones N. Curr. Opin. Genet. Dev. 1999; 9: 55-61Crossref PubMed Scopus (100) Google Scholar). Yap1p involved in oxidative stress response S. Jones N. PubMed Scopus Google W.S. PubMed Google K. S. PubMed Scopus Google W.M. S. PubMed Scopus Google PubMed Scopus Google K. S. A. 1999; PubMed Scopus Google K. S. A. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google and hydroperoxide 1999; PubMed Scopus Google Scholar). Yap1p the transcription of genes encoding for an a W.S. PubMed Google and for of the major facilitator W.S. PubMed Scopus Google Scholar, N. PubMed Scopus Google Scholar). transcription have genes that to by Yap1p 1999; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, H. N. PubMed Scopus Google the of this transcription factor in stress response the of to to an activator protein-1 element in the (4Moye-Rowley W.S. Harshman K.D. Dev. PubMed Scopus Google Scholar, K.D. W.S. PubMed Scopus Google Scholar). is in the and is for Yap1p-mediated regulation of W.S. PubMed Google Scholar). demonstrated that Yap1p with the K. PubMed Scopus Google Scholar). is and contains been to function in an W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). is in the and and transcriptional by Yap1p S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). that the Yap1p response element to the W.M. Jones N. Curr. Opin. Genet. Dev. 1999; 9: 55-61Crossref PubMed Scopus (100) Google of Yap1p is at the of Yap1p the and the but is is the by the with the cysteine-rich domain of Yap1p S. Jones N. A. PubMed Scopus Google Scholar, S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, N. H. S. 1999; PubMed Scopus Google Scholar). domain contains a three of the Yap1p family S. Jones N. A. PubMed Scopus Google Scholar, S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). of the mutation of the of the treatment of the with oxidative agents hydrogen diamide diethylmaleate the in the of Yap1p in the and transcriptional S. Jones N. A. PubMed Scopus Google Scholar, S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, N. H. S. 1999; PubMed Scopus Google Scholar, W.S. 1999; PubMed Scopus Google Scholar). The is to a that is to the of the the of the the of the to Yap1p S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google FLR1 to for an with to multidrug Goffeau A. PubMed Google Scholar). We have demonstrated that FLR1 overexpression confers resistance to and the a drug in for fluconazole N. PubMed Scopus Google Scholar). FLR1 overexpression been to resistance to benomyl and Genet. 1999; PubMed Scopus Google Scholar, N. S. 1999; PubMed Google Scholar, H. H. PubMed Scopus Google demonstrating in We have demonstrated that FLR1 is a transcriptional target of Yap1p and that the FLR1 promoter contains three potential YREs, that the regulation of FLR1 by Yap1p mediated through these N. PubMed Scopus Google Scholar). the we show that the three elements are not equivalent, and important for the optimal transactivation of FLR1 by Yap1p in response to of and alkylating We show that FLR1 overexpression confers resistance to and menadione but hypersensitivity to H2O2, that the Flr1p in to role in oxidative stress response in S. this we have the function of three potential YREs in the FLR1 promoter by with to to FLR1 regulation by Yap1p. of that these three are mutation of of the three YREs the of Yap1p to an demonstrating that the three YREs are to optimal induction of FLR1 by Yap1p. the with each that Yap1p to the three sites mutation of the three YREs the induction of the by Yap1p, we that is in the FLR1 results that the three YREs are not functionally transactivation of the FLR1 promoter with Yap1p, mutation of YRE3 the most in followed by YRE2 and and we show by that Yap1p, and binds to YRE3 to YRE2 and to results that the of the three YREs to in the of Yap1p for each previously YRE3 the and YRE2 to the activator protein-1 element to the in the in of a by Yap1p K. PubMed Scopus Google Scholar). is that factors the of the the the of each the of sites for the of a to of FLR1 by Yap1p. The contains for transcription a at a stress response element at to transcriptional induction in response to oxidative stress H. PubMed Scopus Google and a drug response element at for of the transcription factors and involved in N. S. 1999; PubMed Google Scholar). the of these to Yap1p been to with the transcription factor to the of target genes in response to W.M. S. PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar). not been for is not to this to the FLR1 we that the of the three YREs with the of the FLR1 promoter by and in a of the three YREs to that upon overexpression (YRE3 > YRE2 > YRE2 to important YRE3 for the induction of FLR1 by H2O2, and > YRE3 > the three YREs involved in the induction by (YRE3 YRE2 YRE1). The for these is is that of Yap1p to the FLR1 promoter of factors the of the three YREs in response to results that (i) the contains three functional YREs, (ii) the of and and function the and YREs differentially transcriptional induction by Yap1p in response to Yap1p target genes the is the to three YREs. The and a W.S. PubMed Google Scholar, PubMed Scopus Google Scholar, W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). The contains YREs, but is not YREs are functional are important for the transactivation of by Yap1p S. Jones N. PubMed Scopus Google Scholar). have an by and promoter is to YREs PubMed Scopus Google Scholar). to these YREs are functional and for the regulation of by show that FLR1 transcription is induced by Yap1p upon treatment of the with oxidizing induced by H2O2, and but not by that the induction of FLR1 is for induction is to that for is induced by H2O2, and but not by S. Jones N. PubMed Scopus Google Scholar, W.M. S. PubMed Scopus Google Scholar, PubMed Scopus Google that the genes are by the that to FLR1 and induced by PubMed Scopus Google that Yap1p are differentially in response to is that transcription factors to to these results that FLR1 belongs to the of genes by Yap1p in response to oxidative stress and that this not of and with but of been that yeast to results in of FLR1 S. A. 1999; PubMed Scopus Google Scholar). We show that this at the transcriptional is mediated by Yap1p, and the three YREs The by Yap1p transcription in response to are but to involved in oxidative stress by Yap1p in response to been to of Yap1p to the the of S. Jones N. PubMed Scopus Google Scholar, S. Jones N. A. PubMed Scopus Google Scholar). by the of S. A. 1999; PubMed Scopus Google Scholar). we that plays role in the of FLR1 by is important for the induction of FLR1 by in the of induction by Yap1p in response to and alkylating the of Yap1p is the of FLR1 induction by we have a of and FLR1 not have in the role of Yap1p in the of to a and the of Flr1p to this N. PubMed Scopus Google Scholar). we tested a the FLR1 the of a Our results show that Yap1p overexpression the confers resistance to and to a been that a confers hypersensitivity to and and that confers resistance to S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google but the of Yap1p these not The results that FLR1 is the major target of Yap1p resistance to in S. cerevisiae. results show that confers resistance to and that FLR1 is of the Yap1p this results to the that a major facilitator a of resistance to Flr1p by the of these to PubMed Scopus Google Scholar, A. Google Scholar, A. PubMed Scopus Google by the function of by in the cell to these to of and to to with the of the Flr1p transporter to the the of these and not N. S. 1999; PubMed Google Scholar). and to the of to Flr1p confers are to that Flr1p not function transcriptional been in the of the transporter that that are not transcription of the PubMed Scopus Google Scholar). these that is transporter and we that FLR1 overexpression confers hypersensitivity to is not by FLR1 overexpression of the the to to H2O2, that the of FLR1 are to the to this Yap1p-mediated to been to a of and S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, K. S. A. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar). Our results that Yap1p-mediated response to the of resistance by and hypersensitivity by with the of the resistance that of FLR1 that is the we that overexpression of in in the of FLR1 that of the Yap1p is by the that overexpression in an results in resistance hypersensitivity of Yap1p the have been to resistance to diamide but hypersensitivity to H2O2, the in the of diamide W.S. 1999; PubMed Scopus Google Scholar). is that the hypersensitivity for these results the transactivation of The by FLR1 the to is not this is not to major overexpression of the gene, for a transporter of the family in to diamide resistance but and for to is for FLR1 to by Yap1p and W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). The Saccharomyces cerevisiae transcription factor Yap1p plays an important role in oxidative stress response and multidrug resistance (MDR)1 by activating target genes involved in cellular detoxification (1Bauer B.E. Wolfger H. Kuchler K. Biochim. Biophys. Acta. 1999; 1461: 217-236Crossref PubMed Scopus (228) Google Scholar, 2Toone W.M. Jones N. Curr. Opin. Genet. Dev. 1999; 9: 55-61Crossref PubMed Scopus (100) Google Scholar, 3Kolaczkowska A. Goffeau A. Drug Resist Update. 1999; 2: 403-414Crossref PubMed Scopus (106) Google Scholar). Yap1p belongs to the bZip (basic domain/leucine zipper) family of transcription factors that includes the yeast Gcn4p and the mammalian activator protein-1 proteins Fos and Jun (4Moye-Rowley W.S. Harshman K.D. Dev. PubMed Scopus Google Scholar). transcription by to in the promoter of W.M. Jones N. Curr. Opin. Genet. Dev. 1999; 9: 55-61Crossref PubMed Scopus (100) Google Scholar). Yap1p involved in oxidative stress response S. Jones N. PubMed Scopus Google W.S. PubMed Google K. S. PubMed Scopus Google W.M. S. PubMed Scopus Google PubMed Scopus Google K. S. A. 1999; PubMed Scopus Google K. S. A. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google and hydroperoxide 1999; PubMed Scopus Google Scholar). Yap1p the transcription of genes encoding for an a W.S. PubMed Google and for of the major facilitator W.S. PubMed Scopus Google Scholar, N. PubMed Scopus Google Scholar). transcription have genes that to by Yap1p 1999; PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, H. N. PubMed Scopus Google the of this transcription factor in stress response Yap1p the of to to an activator protein-1 element in the (4Moye-Rowley W.S. Harshman K.D. Dev. PubMed Scopus Google Scholar, K.D. W.S. PubMed Scopus Google Scholar). is in the and is for Yap1p-mediated regulation of W.S. PubMed Google Scholar). demonstrated that Yap1p with the K. PubMed Scopus Google Scholar). is and contains been to function in an W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). is in the and and transcriptional by Yap1p S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). that the Yap1p response element to the W.M. Jones N. Curr. Opin. Genet. Dev. 1999; 9: 55-61Crossref PubMed Scopus (100) Google Scholar). The of Yap1p is at the of Yap1p the and the but is is the by the with the cysteine-rich domain of Yap1p S. Jones N. A. PubMed Scopus Google Scholar, S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, N. H. S. 1999; PubMed Scopus Google Scholar). domain contains a three of the Yap1p family S. Jones N. A. PubMed Scopus Google Scholar, S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). of the mutation of the of the treatment of the with oxidative agents hydrogen diamide diethylmaleate the in the of Yap1p in the and transcriptional S. Jones N. A. PubMed Scopus Google Scholar, S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, N. H. S. 1999; PubMed Scopus Google Scholar, W.S. 1999; PubMed Scopus Google Scholar). The is to a that is to the of the the of the the of the to Yap1p S. N. A. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). The FLR1 to for an with to multidrug Goffeau A. PubMed Google Scholar). We have demonstrated that FLR1 overexpression confers resistance to and the a drug in for fluconazole N. PubMed Scopus Google Scholar). FLR1 overexpression been to resistance to benomyl and Genet. 1999; PubMed Scopus Google Scholar, N. S. 1999; PubMed Google Scholar, H. H. PubMed Scopus Google demonstrating in We have demonstrated that FLR1 is a transcriptional target of Yap1p and that the FLR1 promoter contains three potential YREs, that the regulation of FLR1 by Yap1p mediated through these N. PubMed Scopus Google Scholar). the we show that the three elements are not equivalent, and important for the optimal transactivation of FLR1 by Yap1p in response to of and alkylating We show that FLR1 overexpression confers resistance to and menadione but hypersensitivity to H2O2, that the Flr1p in to role in oxidative stress response in S. cerevisiae. this we have the function of three potential YREs in the FLR1 promoter by with to to FLR1 regulation by Yap1p. of that these three are mutation of of the three YREs the of Yap1p to an demonstrating that the three YREs are to optimal induction of FLR1 by Yap1p. the with each that Yap1p to the three sites mutation of the three YREs the induction of the by Yap1p, we that is in the FLR1 results that the three YREs are not functionally transactivation of the FLR1 promoter with Yap1p, mutation of YRE3 the most in followed by YRE2 and and we show by that Yap1p, and binds to YRE3 to YRE2 and to results that the of the three YREs to in the of Yap1p for each previously YRE3 the and YRE2 to the activator protein-1 element to the in the in of a by Yap1p K. PubMed Scopus Google Scholar). is that factors the of the the the of each the of sites for the of a to of FLR1 by Yap1p. The contains for transcription a at a stress response element at to transcriptional induction in response to oxidative stress H. PubMed Scopus Google and a drug response element at for of the transcription factors and involved in N. S. 1999; PubMed Google Scholar). the of these to Yap1p been to with the transcription factor to the of target genes in response to W.M. S. PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar). not been for is not to this to the FLR1 we that the of the three YREs with the of the FLR1 promoter by and in a of the three YREs to that upon overexpression (YRE3 > YRE2 > YRE2 to important YRE3 for the induction of FLR1 by H2O2, and > YRE3 > the three YREs involved in the induction by (YRE3 YRE2 YRE1). The for these is is that of Yap1p to the FLR1 promoter of factors the of the three YREs in response to results that (i) the contains three functional YREs, (ii) the of and and function the and YREs differentially transcriptional induction by Yap1p in response to Yap1p target genes the is the to three YREs. The and a W.S. PubMed Google Scholar, PubMed Scopus Google Scholar, W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). The contains YREs, but is not YREs are functional are important for the transactivation of by Yap1p S. Jones N. PubMed Scopus Google Scholar). have an by and promoter is to YREs PubMed Scopus Google Scholar). to these YREs are functional and for the regulation of by show that FLR1 transcription is induced by Yap1p upon treatment of the with oxidizing induced by H2O2, and but not by that the induction of FLR1 is for induction is to that for is induced by H2O2, and but not by S. Jones N. PubMed Scopus Google Scholar, W.M. S. PubMed Scopus Google Scholar, PubMed Scopus Google that the genes are by the that to FLR1 and induced by PubMed Scopus Google that Yap1p are differentially in response to is that transcription factors to to these results that FLR1 belongs to the of genes by Yap1p in response to oxidative stress and that this not of and with but of been that yeast to results in of FLR1 S. A. 1999; PubMed Scopus Google Scholar). We show that this at the transcriptional is mediated by Yap1p, and the three YREs The by Yap1p transcription in response to are but to involved in oxidative stress by Yap1p in response to been to of Yap1p to the the of S. Jones N. PubMed Scopus Google Scholar, S. Jones N. A. PubMed Scopus Google Scholar). by the of S. A. 1999; PubMed Scopus Google Scholar). we that plays role in the of FLR1 by is important for the induction of FLR1 by in the of induction by Yap1p in response to and alkylating the of Yap1p is the of FLR1 induction by we have a of and FLR1 not have in the role of Yap1p in the of to a and the of Flr1p to this N. PubMed Scopus Google Scholar). we tested a the FLR1 the of a Our results show that Yap1p overexpression the confers resistance to and to a been that a confers hypersensitivity to and and that confers resistance to S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google but the of Yap1p these not The results that FLR1 is the major target of Yap1p resistance to in S. cerevisiae. results show that confers resistance to and that FLR1 is of the Yap1p this results to the that a major facilitator a of resistance to Flr1p by the of these to PubMed Scopus Google Scholar, A. Google Scholar, A. PubMed Scopus Google by the function of by in the cell to these to of and to to with the of the Flr1p transporter to the the of these and not N. S. 1999; PubMed Google Scholar). and to the of to Flr1p confers are to that Flr1p not function transcriptional been in the of the transporter that that are not transcription of the PubMed Scopus Google Scholar). these that is transporter and we that FLR1 overexpression confers hypersensitivity to is not by FLR1 overexpression of the the to to H2O2, that the of FLR1 are to the to this Yap1p-mediated to been to a of and S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, K. S. A. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar). Our results that Yap1p-mediated response to the of resistance by and hypersensitivity by with the of the resistance that of FLR1 that is the we that overexpression of in in the of FLR1 that of the Yap1p is by the that overexpression in an results in resistance hypersensitivity of Yap1p the have been to resistance to diamide but hypersensitivity to H2O2, the in the of diamide W.S. 1999; PubMed Scopus Google Scholar). is that the hypersensitivity for these results the transactivation of The by FLR1 the to is not this is not to major overexpression of the gene, for a transporter of the family in to diamide resistance but and for to is for FLR1 to by Yap1p and W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). this we have the function of three potential YREs in the FLR1 promoter by with to to FLR1 regulation by Yap1p. of that these three are mutation of of the three YREs the of Yap1p to an demonstrating that the three YREs are to optimal induction of FLR1 by Yap1p. the with each that Yap1p to the three sites mutation of the three YREs the induction of the by Yap1p, we that is in the FLR1 Our results that the three YREs are not functionally transactivation of the FLR1 promoter with Yap1p, mutation of YRE3 the most in followed by YRE2 and and we show by that Yap1p, and binds to YRE3 to YRE2 and to results that the of the three YREs to in the of Yap1p for each previously YRE3 the and YRE2 to the activator protein-1 element to the in the in of a by Yap1p K. PubMed Scopus Google Scholar). is that factors the of the the the of each the of sites for the of a to of FLR1 by Yap1p. The contains for transcription a at a stress response element at to transcriptional induction in response to oxidative stress H. PubMed Scopus Google and a drug response element at for of the transcription factors and involved in N. S. 1999; PubMed Google Scholar). the of these to Yap1p been to with the transcription factor to the of target genes in response to W.M. S. PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar). not been for is not to this to the FLR1 we that the of the three YREs with the of the FLR1 promoter by and in a of the three YREs to that upon overexpression (YRE3 > YRE2 > YRE2 to important YRE3 for the induction of FLR1 by H2O2, and > YRE3 > the three YREs involved in the induction by (YRE3 YRE2 YRE1). The for these is is that of Yap1p to the FLR1 promoter of factors the of the three YREs in response to results that (i) the contains three functional YREs, (ii) the of and and function the and YREs differentially transcriptional induction by Yap1p in response to Yap1p target genes the is the to three YREs. The and a W.S. PubMed Google Scholar, PubMed Scopus Google Scholar, W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). The contains YREs, but is not YREs are functional are important for the transactivation of by Yap1p S. Jones N. PubMed Scopus Google Scholar). have an by and promoter is to YREs PubMed Scopus Google Scholar). to these YREs are functional and for the regulation of by Yap1p. We show that FLR1 transcription is induced by Yap1p upon treatment of the with oxidizing induced by H2O2, and but not by that the induction of FLR1 is for induction is to that for is induced by H2O2, and but not by S. Jones N. PubMed Scopus Google Scholar, W.M. S. PubMed Scopus Google Scholar, PubMed Scopus Google that the genes are by the that to FLR1 and induced by PubMed Scopus Google that Yap1p are differentially in response to is that transcription factors to to these results that FLR1 belongs to the of genes by Yap1p in response to oxidative stress and that this not of and with but of been that yeast to results in of FLR1 S. A. 1999; PubMed Scopus Google Scholar). We show that this at the transcriptional is mediated by Yap1p, and the three YREs The by Yap1p transcription in response to are but to involved in oxidative stress by Yap1p in response to been to of Yap1p to the the of S. Jones N. PubMed Scopus Google Scholar, S. Jones N. A. PubMed Scopus Google Scholar). by the of S. A. 1999; PubMed Scopus Google Scholar). we that plays role in the of FLR1 by is important for the induction of FLR1 by in the of induction by Yap1p in response to and alkylating the of Yap1p is To the of FLR1 induction by we have a of and FLR1 not have in the role of Yap1p in the of to a and the of Flr1p to this N. PubMed Scopus Google Scholar). we tested a the FLR1 the of a Our results show that Yap1p overexpression the confers resistance to and to a been that a confers hypersensitivity to and and that confers resistance to S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google but the of Yap1p these not The results that FLR1 is the major target of Yap1p resistance to in S. cerevisiae. results show that confers resistance to and that FLR1 is of the Yap1p this results to the that a major facilitator a of resistance to Flr1p by the of these to PubMed Scopus Google Scholar, A. Google Scholar, A. PubMed Scopus Google by the function of by in the cell to these to The of and to to with the of the Flr1p transporter to the the of these and not N. S. 1999; PubMed Google Scholar). and to the of to Flr1p confers are to that Flr1p not function transcriptional been in the of the transporter that that are not transcription of the PubMed Scopus Google Scholar). these that is transporter and Finally, we that FLR1 overexpression confers hypersensitivity to is not by FLR1 overexpression of the the to to H2O2, that the of FLR1 are to the to this Yap1p-mediated to been to a of and S. Jones N. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, K. S. A. 1999; PubMed Scopus Google Scholar, 1999; PubMed Scopus Google Scholar). Our results that Yap1p-mediated response to the of resistance by and hypersensitivity by with the of the resistance that of FLR1 that is the we that overexpression of in in the of FLR1 that of the Yap1p is by the that overexpression in an results in resistance hypersensitivity of Yap1p the have been to resistance to diamide but hypersensitivity to H2O2, the in the of diamide W.S. 1999; PubMed Scopus Google Scholar). is that the hypersensitivity for these results the transactivation of The by FLR1 the to is not this is not to major overexpression of the gene, for a transporter of the family in to diamide resistance but and for to is for FLR1 to by Yap1p and W.S. PubMed Google Scholar, W.S. PubMed Scopus Google Scholar). We are to for reading the

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