Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae

Orna Carmel-Harel, Robert Stearman, Audrey P. Gasch, David Botstein, Patrick O. Brown, Gisela Storz

Research output: Contribution to journalArticle

87 Citations (Scopus)

Abstract

The Saccharomyces cerevisiae Yap1p transcription factor is required for the H2O2-dependent activation of many antioxidant genes including the TRX2 gene encoding thioredoxin 2. To identify factors that regulate Yap1p activity, we carried out a genetic screen for mutants that show elevated expression of a TRX2-HIS3 fusion in the absence of H2O2. Two independent mutants isolated in this screen carried mutations in the TRR1 gene encoding thioredoxin reductase. Northern blot and whole-genome expression analysis revealed that the basal expression of most Yap1p targets and many other H2O2-inducible genes is elevated in Δtrr1 mutants in the absence of external stress. In Δtrr1 mutants treated with H2O2, the Yap1p targets, as well as genes comprising a general environmental stress response and genes encoding protein-folding chaperones, are hyperinduced. However, despite the elevated expression of genes encoding antioxidant enzymes, Δtrr1 mutants are extremely sensitive to H2O2. The results suggest that cells lacking thioredoxin reductase have diminished capacity to detoxify oxidants and/or to repair oxidative stress-induced damage and that the thioredoxin system is involved in the redox regulation of Yap1p transcriptional activity.

Original languageEnglish (US)
Pages (from-to)595-605
Number of pages11
JournalMolecular Microbiology
Volume39
Issue number3
DOIs
StatePublished - 2001
Externally publishedYes

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Thioredoxin-Disulfide Reductase
Saccharomyces cerevisiae
Oxidative Stress
Thioredoxins
Genes
Antioxidants
Protein Folding
Oxidants
Northern Blotting
Oxidation-Reduction
Transcription Factors
Genome
Gene Expression
Mutation
Enzymes
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae. / Carmel-Harel, Orna; Stearman, Robert; Gasch, Audrey P.; Botstein, David; Brown, Patrick O.; Storz, Gisela.

In: Molecular Microbiology, Vol. 39, No. 3, 2001, p. 595-605.

Research output: Contribution to journalArticle

Carmel-Harel, Orna ; Stearman, Robert ; Gasch, Audrey P. ; Botstein, David ; Brown, Patrick O. ; Storz, Gisela. / Role of thioredoxin reductase in the Yap1p-dependent response to oxidative stress in Saccharomyces cerevisiae. In: Molecular Microbiology. 2001 ; Vol. 39, No. 3. pp. 595-605.
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