Genetic Analysis of Glutathione Peroxidase in Oxidative Stress Response of Saccharomyces cerevisiae

Three glutathione peroxidase homologs (YKL026C, YBR244W, and YIR037W/HYR1) were found in the Saccharomyces Genome Database. We named them GPX1, GPX2, and GPX3, respectively, and we investigated the function of each gene product. The gpx3Δ mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes. Glutathione peroxidase activity decreased approximately 57 and 93% in the gpx3Δ and gpx1Δ/gpx2Δ/gpx3Δ mutants, respectively, compared with that of wild type. Expression of the GPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation. The GPX2 gene expression was induced by oxidative stress, which was dependent upon the Yap1p. The TSA1 (thiol-specific antioxidant) gene encodes thioredoxin peroxidase that can reduce peroxides by using thioredoxin as a reducing power. Disruption of the TSA1 gene enhanced the basal expression level of the Yap1p target genes such as GSH1, GLR1, and GPX2 and that resulted in increases of total glutathione level and activities of glutathione reductase and glutathione peroxidase. However, expression of the TSA1 gene did not increase in the gpx1Δ/gpx2Δ/gpx3Δ mutant. Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Δ mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase. Three glutathione peroxidase homologs (YKL026C, YBR244W, and YIR037W/HYR1) were found in the Saccharomyces Genome Database. We named them GPX1, GPX2, and GPX3, respectively, and we investigated the function of each gene product. The gpx3Δ mutant was hypersensitive to peroxides, whereas null mutants of the GPX1 and GPX2 did not show any obvious phenotypes. Glutathione peroxidase activity decreased approximately 57 and 93% in the gpx3Δ and gpx1Δ/gpx2Δ/gpx3Δ mutants, respectively, compared with that of wild type. Expression of the GPX3 gene was not induced by any stresses tested, whereas that of the GPX1 gene was induced by glucose starvation. The GPX2 gene expression was induced by oxidative stress, which was dependent upon the Yap1p. The TSA1 (thiol-specific antioxidant) gene encodes thioredoxin peroxidase that can reduce peroxides by using thioredoxin as a reducing power. Disruption of the TSA1 gene enhanced the basal expression level of the Yap1p target genes such as GSH1, GLR1, and GPX2 and that resulted in increases of total glutathione level and activities of glutathione reductase and glutathione peroxidase. However, expression of the TSA1 gene did not increase in the gpx1Δ/gpx2Δ/gpx3Δ mutant. Therefore, de novo synthesis and recycling of glutathione were increased in the tsa1Δ mutant to maintain the catalytic cycle of glutathione peroxidase reaction efficiently as a backup system for thioredoxin peroxidase. glutathione peroxidase thioredoxin peroxidase lipid hydroperoxide tert-butyl hydroperoxide Yap1p response element base pairs polymerase chain reaction stress response element heat shock protein All aerobic organisms use molecular oxygen for respiration or oxidation of nutrients to acquire the energy efficiently. Molecular oxygen is reduced to H2O through acceptance of four electrons. During the reduction of molecular oxygen, several reactive oxygen species are formed, i.e. acceptance of one, two, and three electrons to form, respectively, superoxide anion radical (O⨪2), hydrogen peroxide (H2O2), and hydroxyl radical (HO⋅). These reactive oxygen species attack almost all cell components, DNA, protein, and lipid membrane, and they sometimes cause lethal damage to the cells. Among the reactive oxygen species, HO⋅ as well as perhydroxyl radical (HOO⋅) can extract bis-allylic hydrogen atom of unsaturated fatty acid (LH) to form lipid alkyl radical (L⋅) (1Aikens J. Dix T.A. J. Biol. Chem. 1991; 266: 15091-15098Abstract Full Text PDF PubMed Google Scholar). The L⋅ is oxidized by molecular oxygen to generate a lipid peroxy radical (LOO⋅), and the LOO⋅ thus formed reacts with LH to give lipid hydroperoxide (LOOH) and L⋅. A radical chain reaction is then propagated. LOOH also belongs to the reactive oxygen species, and the occurrence of the LOOHs in biological membranes may be one of the major oxidative damages to the cells. Because reactive oxygen species are commonplace in aerobic organisms, they have enzymatic as well as non-enzymatic defense systems. For example, superoxide dismutase catalyzes disproportions of O⨪2to O2 and H2O2, and H2O2 thus formed is decomposed to H2O and O2 by catalase. H2O2 as well as LOOH are reduced to H2O and corresponding alcohol by glutathione peroxidase (GPx).1 Ascorbate can also work as a reductant for ascorbate peroxidase in plants (2Asada K. Scandalios J.G. Oxidative Stress and the Molecular Biology of Antioxidant Defenses. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1997: 715-735Google Scholar). β-Carotene and tocopherol function as radical scavengers. Glutathione is also a major antioxidant in aerobic cells. However, it has been widely believed that microorganisms do not have peroxidases whose electron donor is glutathione. Microorganisms are believed to use cytochrome c as an electron donor for the peroxidase reaction (cytochrome c peroxidase). GPx has been thought to be evolutionarily acquired by mammals. However, we have demonstrated that yeasts have GPx and that glutathione plays a crucial role in the defense line against reactive oxygen species. For example, we have previously shown that catalase-deficient (ctt1Δ/cta1Δ) mutant of Saccharomyces cerevisiae showed almost the same sensitivity to H2O2 compared with that of wild type, although the gsh1-deficient mutant was hypersensitive to H2O2 and could not show an adaptive response to oxidative stress (3Izawa S. Inoue Y. Kimura A. FEBS Lett. 1995; 368: 73-76Crossref PubMed Scopus (225) Google Scholar, 4Izawa S. Inoue Y. Kimura A. Biochem. J. 1996; 320: 61-67Crossref PubMed Scopus (203) Google Scholar). The GSH1 gene encodes γ-glutamylcysteine synthetase which is a rate-limiting enzyme for glutathione biosynthesis. Additionally, we purified GPx from the yeast Hansenula mrakii (5Tran L.-T. Inoue Y. Kimura A. Biochim. Biophys. Acta. 1993; 1164: PubMed Scopus Google Scholar). The GPx of mrakii was found in the and the of which is an a of reactive oxygen species are oxygen respiration Y. L.-T. S. Y. Kimura A. Biochim. Biophys. Acta. 1995; PubMed Scopus Google Scholar). We mrakii as a yeast by Y. K. L.-T. K. Kimura A. Biol. Chem. Scopus Google and the mutants from mrakii could not GPx the oxidative stress Y. L.-T. Kimura A. J. 1993; Scopus Google Scholar). we have been that yeasts also have the GPx Y. Kimura A. in and Scholar). We the Saccharomyces Genome base for GPx and we found three (YKL026C, YBR244W, and of has been to the peroxide gene in the base although function has not been we them GPX1, GPX2, and GPX3, respectively, and each gene to the through of with to the oxidative stress The TSA1 gene has been as a which synthetase from oxidative in S. cerevisiae K. J. Biol. Chem. Full Text PDF PubMed Google Scholar). was found to have peroxidase activity in with thioredoxin as a reducing i.e. thioredoxin peroxidase K. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). have been widely from of from of yeasts to and they a K. S. A. PubMed Scopus Google Scholar, Google Scholar). can reduce H2O2 and LOOH in the of thioredoxin in reduced form, and oxidized form of thioredoxin is reduced by thioredoxin reductase with catalytic cycle is to that of i.e. GPx LOOH in the of reduced and oxidized glutathione is reduced by glutathione reductase by using as a reducing power. reaction is oxidized to and thus formed is reduced to by an of we also the the GPx system and the system in oxidative stress and we that GPx is as a backup system for in S. S. cerevisiae a was from the of and was as a wild All in were the of the The GPX1 gene was by using the as and The and were to the and The the GPX1 gene was with and and to which was by and and then by to The was with and with and then the gene was to The was by was to in the and and the was to the GPX1 The was The GPX2 gene was by the and were to have the The the gene was with by and then to which was by and to give The was with and by with and the gene was to give The was with and and the was to the GPX2 The was The GPX3 gene was by the and The and were to the and The the GPX3 gene was by and and to the and of to The was with and and the gene was to The was with and and the was to the GPX3 The was The TSA1 gene was by using the and The TSA1 gene was with and and then to of The was with and by with and the gene was to give The was with and and the was to the TSA1 The was The mutant was by using the A. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar). The was as previously Y. Y. Kimura A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). were in and were with of each was H2O2 or and for were in approximately by and with were in and with were for and the were as cell GPx activity was in a reaction in glutathione reductase and cell the of the reaction was for and the reaction was by the of of was for Three were for each for GPx glutathione was from the reaction which was to was to the reaction of non-enzymatic cell were from the reaction the GPx activity in cell the was of the activity was as the of enzyme of glutathione for was was by the of Biochem. PubMed Scopus Google Scholar). the of several stresses expression of the of S. cerevisiae were in approximately and then of were the of stress was to the For heat shock the was to an and then the was For the were by with in glucose and each total was to the of T.A. PubMed Scopus Google Scholar). gene was by using a and as a the of Yap1p expression of the were in with and approximately and the total was as were in to and cell were as were by and were to in was as the and with peroxidase was as the was to oxidation level of yeast was using the S. A. 1996; PubMed Scopus Google Scholar). in were and in for were in and with by for were in of and was with and using a The of was by protein in the The GSH1 to the of the was by using the and were to the and the by was with and the of the of the J. PubMed Scopus Google to a of the acid of were to whose were The in the was by with and the of to The were in with and for A of the was to a of and with approximately the of stress H2O2 was to of and was for were as and activity was as by in Molecular Cold Spring Harbor Laboratory, Cold Spring Harbor, Scholar). of the activity was as the of enzyme S. A. J. PubMed Scopus Google was by and and to the and of PubMed Google Scholar). The was to the of wild and tsa1Δ DNA, the were with We the Saccharomyces Genome base for the homologs of and we found three that i.e. YBR244W, and We named them GPX1, GPX2, and GPX3, of the was to the and in and was to as the peroxide gene although of the gene has not been the of the acid from the of each GPx gene from S. cerevisiae and that of A. PubMed Scopus Google Scholar). has been that have a in and the corresponding to the is which is as a A. PubMed Scopus Google Scholar). the in the of S. cerevisiae GPx was of and the was in three GPx homologs the of in The acid the was GPx and yeast although in was not compared with the the GPx and yeast GPx homologs was approximately the yeast homologs was compared with and the are and and and and The molecular of a of from is approximately and the of a Biochem. J. PubMed Scopus Google Scholar). The molecular of and in S. cerevisiae were to be and respectively, which was of We have previously purified GPx from a yeast mrakii (5Tran L.-T. Inoue Y. Kimura A. Biochim. Biophys. Acta. 1993; 1164: PubMed Scopus Google Scholar). The molecular of the enzyme was by Because the GPx of mrakii was to the cell and were to we could not the molecular of the enzyme by a the of the yeast enzyme has not been GPx gene was by and gene was in i.e. and and and was in mutants, and of them stress was the same as that of wild of the mutant are shown in shown in the gpx3Δ mutant was to H2O2 and tert-butyl hydroperoxide which was as a for and are for from mammals. Disruption of the GPX1 or GPX2 or of them did not the sensitivity to peroxides, although of the GPX3 gene in enhanced the of mutants against for are and was of GPx genes to glutathione the enzyme activity was are several the activity in S. the yeasts were in the of or A. Biochem. Biophys. PubMed Scopus Google Scholar, K. Kimura A. Biol. Chem. Scholar). However, the activity in such not the GPx activity in the cell with and of which are can the GPx has been well that the can activity A. Biochem. PubMed Scopus Google Scholar, A. Biochem. PubMed Scopus Google Scholar). the GPx activity we the the of any and we three for each as and shown in the enzyme activity decreased approximately in the gpx3Δ and it was in the gpx1Δ/gpx2Δ/gpx3Δ mutant compared with that of wild with the of the GPX3 gene is thought to be the major GPx that peroxides in S. The expression of each gene several stress was by shown in the basal expression level of the GPX3 gene was compared with of although expression was not induced by any stresses The expression level of the GPX1 gene was induced the and are and heat shock also induced the expression of Expression of the GPX2 gene was induced by several oxidative stresses such as and the GPx activity was increased the were to oxidative stress of the expression of Yap1p target gene in the tsa1Δ mutant is dependent upon the Yap1p. were in to and with or for activity from the GPx the of three wild Yap1p is a in the oxidative stress response in S. cerevisiae Full Text PDF PubMed Scopus Google Scholar, PubMed Scopus Google Scholar). Yap1p and to the response K. Biol. PubMed Scopus Google Scholar). The GPX2 gene has three in from the and expression of the GPX2 gene is by basal expression level of the GPX2 gene was in the mutant and in the shown in basal expression level of the GPX2 gene decreased in the whereas it increased in the the oxidative expression of the GPX2 gene was in the mutant These that expression of the GPX2 gene is the of Yap1p. Expression of the GPX1 gene was induced by the although the of Yap1p in the did not the basal expression level of it Additionally, was found in the GPX1 Yap1p is not to be in the of the GPX1 the expression level of the GPX3 gene did not in the or of Yap1p in the cell The TSA1 gene (thiol-specific antioxidant) encodes a peroxidase whose electron donor is thioredoxin thioredoxin K. J. Biol. Chem. 1993; Full Text PDF PubMed Google Scholar, J. Biol. Chem. Full Text PDF PubMed Google Scholar, J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar). to the GPx and in the oxidative stress response in the TSA1 gene was and sensitivity to the peroxides was shown in the tsa1Δ mutant was to H2O2 not to of tsa1Δ with gpx1Δ/gpx2Δ/gpx3Δ was not although such a mutant was to H2O2 and the of tsa1Δ and gpx1Δ/gpx2Δ/gpx3Δ mutants in any The tsa1Δ mutant showed and such a was enhanced in the mutant. was also in the the of of the TSA1 gene the GPx the enzyme activity was shown in GPx activity increased approximately in the tsa1Δ mutant compared with that of wild type. was to which gene expression was The basal expression level of GPX2 was increased in the tsa1Δ whereas of genes were not Therefore, increase of the GPx activity in the tsa1Δ mutant was found to be to the increased level of GPX2 gene We then TSA1 gene expression is increased in the gpx1Δ/gpx2Δ/gpx3Δ mutant. shown in of the gene did not the basal expression level of the TSA1 of null expression of the Yap1p target was from the tsa1Δ mutant or mutant and was The GPX2 gene expression was increased in the tsa1Δ the GPX2 gene was the target for the Yap1p three The gene is also the Yap1p target and basal expression level increased in the tsa1Δ mutant. Disruption of the genes did not the of the TSA1 and wild for the catalytic cycle of the GPx reaction to a of reduced glutathione is We the activity of glutathione which is a major enzyme the reduction of glutathione to reduced glutathione. The enzyme activity was increased in the tsa1Δ mutant We also the glutathione activity by using the The GSH1 gene is a rate-limiting enzyme for the de novo synthesis of glutathione in S. cerevisiae Y. K. S. Kimura A. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). shown in the basal expression level of the gene increased in the tsa1Δ mutant. We also the increase of the GSH1 level by not total glutathione level in the tsa1Δ mutant was increased type, These that GPx is as a backup system for and de novo synthesis and recycling of glutathione were in the tsa1Δ mutant to maintain the catalytic cycle of GPx reaction efficiently. shown in and of the TSA1 gene the de novo synthesis and recycling of glutathione as well as expression of the GPX2 Glutathione reductase is by the and expression is dependent upon Yap1p 1996; PubMed Scopus Google Scholar). The GSH1 gene is also a target gene for Yap1p A. Biol. PubMed Google and we demonstrated that the GPX2 gene is one of These that of the TSA1 gene the activity of Yap1p. has been that Yap1p is in and the are the the are to oxidative stress, Yap1p is in the and expression of target genes is enhanced S. A. J. PubMed Scopus Google Scholar). The in the oxidative expression of the Yap1p target genes is thought to be the of Yap1p S. A. PubMed Scopus Google Yap1p protein level activity of Yap1p increases oxidative stress response S. A. J. PubMed Scopus Google Scholar, K. FEBS Lett. PubMed Scopus Google Scholar, J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the of expression level and corresponding enzyme activity of the Yap1p target genes in the tsa1Δ several can be is that peroxides are in the by of the TSA1 oxidative stress, and the of Yap1p is to the of target the of the tsa1Δ mutant is reduced compared with that of wild in the of oxidative stress be to be to the of reactive oxygen species in the cells. we oxidation level and the of Yap1p in the by using shown in oxidation in the tsa1Δ mutant and the gpx1Δ/gpx2Δ/gpx3Δ mutant were not increased compared with that of wild of in the was not in the tsa1Δ mutant as as we investigated in the of Yap1p was the wild and tsa1Δ mutant by not The basal expression level of the which encodes thioredoxin reductase and is a target for the Yap1p J. Biol. Chem. Full Text PDF PubMed Google Scholar, S. J. PubMed Scopus Google was increased in the tsa1Δ mutant not in the gpx1Δ/gpx2Δ/gpx3Δ mutant The of S. J. PubMed Scopus Google and the J. Biol. Chem. Full Text PDF PubMed Google which are also the for the are increased in the tsa1Δ mutant not Therefore, function of the Yap1p to be in the tsa1Δ it is not to be dependent upon the of Yap1p of of protein was by was by wild We investigated expression of the Yap1p target gene is increased or not in the tsa1Δ mutant the are to oxidative shown in activity from the gene was increased by the oxidative stress in the tsa1Δ mutant as well as in the wild The GPx activity was also increased in the tsa1Δ mutant by oxidative stress Therefore, the increase of the basal expression of the Yap1p target genes in the tsa1Δ mutant is not i.e. the genes to be the oxidative stress We then the mutant to the increase of the basal expression of Yap1p target genes is by Yap1p or Because GSH1 is a target for the basal expression level of the gene decreased in the it did not increase in the mutant compared with that in the mutant Additionally, activity from the gene was increased by of the mutant with were in the of GPx activity Therefore, we that increase of the basal expression of the Yap1p target genes in the tsa1Δ mutant was dependent upon the it was not in the We have been the oxidative stress response in yeast and that glutathione plays a crucial role in the and of to oxidative stress in yeast (3Izawa S. Inoue Y. Kimura A. FEBS Lett. 1995; 368: 73-76Crossref PubMed Scopus (225) Google Scholar). it has been widely believed that microorganisms do not have we purified and GPx from the yeast mrakii (5Tran L.-T. Inoue Y. Kimura A. Biochim. Biophys. Acta. 1993; 1164: PubMed Scopus Google Scholar, Y. L.-T. S. Y. Kimura A. Biochim. Biophys. Acta. 1995; PubMed Scopus Google Scholar, Y. Kimura A. in and Scholar). We then the to three GPx homologs found in the Saccharomyces Genome base to glutathione peroxidase in S. have been to in A. PubMed Scopus Google although was not the for the yeast of the chain is a The corresponding to is which is as a the of yeast was of the been in the GPx such a has not been as the by the have been in and Biochem. 1996; Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 1991; 266: Full Text PDF PubMed Google Scholar). of them are such as in J. PubMed Scopus Google thioredoxin reductase S. A. 1996; PubMed Scopus Google and GPx A. PubMed Scopus Google in and one is has been that a to the is for of the chain in J. A. J. PubMed Scopus Google Scholar, J. A. S. A. PubMed Scopus Google Scholar). of a is and although it is approximately from the in the in the of Y. 1991; PubMed Scopus Google Scholar). We for a the and in the of each although such a was J. J. Biochem. PubMed Scopus Google that GPx whose was to the enzyme the activity was from the acid from the of each yeast are thought to be a we have purified GPx from the yeast mrakii (5Tran L.-T. Inoue Y. Kimura A. Biochim. Biophys. Acta. 1993; 1164: PubMed Scopus Google Scholar). The GPx was alkyl we do not have any the the the GPX3 gene may be H2O2 and LOOH the gpx3Δ mutant was hypersensitive to of them The basal level of GPX3 was of and the gpx3Δ mutant was hypersensitive to peroxides, whereas of the GPX1 or GPX2 did not show any obvious with to the to oxidative the GPX3 gene may be a major GPx in S. GPx activity was in the gpx1Δ/gpx2Δ/gpx3Δ mutant in the gpx3Δ mutant have been to of a Biochem. J. PubMed Scopus Google Scholar, Biochem. 1996; PubMed Scopus Google although the of the GPx from mrakii has not been (5Tran L.-T. Inoue Y. Kimura A. Biochim. Biophys. Acta. 1993; 1164: PubMed Scopus Google Scholar). We a that in S. cerevisiae may form a three molecular species in a to the of the of three in yeast expression of each gene several stress was Expression level of the GPX3 gene was compared with of and it was not induced by any stresses as as we Disruption of the GPX3 gene enhanced to peroxides thus the is thought to be a major GPx in peroxides in S. the expression of the GPX2 gene was induced by oxidative stress in the Additionally, response or was found in the GPX2 gene from genes heat shock protein in S. such as and have the heat shock element J. PubMed Scopus Google Scholar, 1995; PubMed Scopus Google Scholar, J. 1993; PubMed Scopus Google Scholar). genes also have been to in and and are in the of the genes Y. Y. Kimura A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar, A. J. 1996; PubMed Scopus Google Scholar). Expression of such genes is induced by a of such as stress and oxidative stress as well as heat and stress are thought to be the J. PubMed Scopus Google Scholar). Expression of the GPX2 gene was induced by oxidative stress, stresses such as heat shock and stress did not the expression of the GPX2 gene as as the oxidative stress did Expression of the GPX1 gene was induced the were to is in glucose J. PubMed Scopus Google Scholar, PubMed Scopus Google Scholar, S. A. 1995; PubMed Scopus Google and an by a Biol. PubMed Scopus Google Scholar). A is of the of the GPX1 The TSA1 gene has been to be as a and belongs to a of Google Scholar). in S. cerevisiae has been thought to H2O2 alkyl peroxides J. Biol. Chem. Full Text PDF PubMed Google Scholar). The tsa1Δ mutant hypersensitive to H2O2 not to which such the K. PubMed Scopus Google that purified could reduce to almost the same as that for in We demonstrated in that basal expression level of the GPX2 gene increased in the tsa1Δ which resulted in increase of the GPx activity GPx purified from mrakii was to alkyl hydroperoxide and L.-T. Inoue Y. Kimura A. Biochim. Biophys. Acta. 1993; 1164: PubMed Scopus Google Scholar). Therefore, the the tsa1Δ mutant did not hypersensitive to could be that the of which was to the increase of GPX2 gene the to to with the catalytic cycle of GPx an of glutathione be the tsa1Δ the de novo synthesis and recycling of glutathione were enhanced glutathione level was also increased in the tsa1Δ mutant. These to be for catalytic cycle of GPx reaction with of GPx in the tsa1Δ GPx is as a backup system for in S. We also activity in the and mutants it can also as a backup system for was not of the tsa1Δ mutant that be is the increase of the basal expression of the Yap1p target genes and Among three the GPX2 gene was found to be by Yap1p and basal expression of it increased in the tsa1Δ mutant we found that the mutant of Yap1p in the that resulted in an increase of basal expression of the Yap1p target genes S. K. K. J. Inoue Y. Kimura A. J. Biol. Chem. Full Text Full Text PDF Scopus Google Scholar). the thioredoxin null oxidation level increased approximately was not the for the tsa1Δ mutant the of increased level of the gene expression was was the mutant was to oxidative stress S. K. K. J. Inoue Y. Kimura A. J. Biol. Chem. Full Text Full Text PDF Scopus Google Scholar). However, in the of tsa1Δ oxidative expression of the gene as well as increase of the GPx activity were is that increase of the basal expression of Yap1p target genes in the tsa1Δ mutant is dependent upon the such an increase was not in the mutant we that of activity to or for of target or to be enhanced in the tsa1Δ mutant by an of several can be that can the function of Yap1p are by gene or that the activity of Yap1p are by The peroxides by using thioredoxin as a reducing in thus the TSA1 gene is to with thioredoxin in we found that of null of the Yap1p and thioredoxin was lethal S. K. K. J. Inoue Y. Kimura A. J. Biol. Chem. Full Text Full Text PDF Scopus Google the mutant was Therefore, of thioredoxin or with to the basal expression of the Yap1p target and and thioredoxin are in the same antioxidant system may the of the function of Yap1p. We S. for and S. for and We also J. and