Thioredoxin Deficiency Causes the Constitutive Activation of Yap1, an AP-1-like Transcription Factor in Saccharomyces cerevisiae

Izawa, Shingo; Maeda, Keiko; Sugiyama, Keiichi; Mano, Junichi; Inoue, Yoshiharu; Kimura, Akira

doi:10.1074/jbc.274.40.28459

Cited by 130 publications

(116 citation statements)

References 49 publications

(37 reference statements)

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“…Reporter Genes-Construction of GSH1-lacZ fusion (pCGSH1-lacZ) and GSH2-lacZ fusion (pCGHS2-lacZ2) clones in the single copy vector YCp50 (25) was described previously (13,21,22). The artificial Yap1p-dependent lacZ reporter gene construct containing three SV40 AP-1 sites and the TATA box of the CYC1 promoter was also used to monitor Yap1p activity (8,11,26).…”

Section: Methodsmentioning

confidence: 99%

“…Localization of Yap1p in the nucleus is controlled by Crm1p-mediated nuclear export through the nuclear export sequence (11,12). The C terminus of Yap1p contains a cysteine-rich domain where three Cys-Ser-Glu sequence motifs may be redox sensors (8,12,13). Because the cysteine-rich domain partially overlaps the nuclear export sequence, deletion of the cysteine-rich domain causes constitutive localization of Yap1p in the nucleus (8).…”

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confidence: 99%

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The Yap1p-dependent Induction of Glutathione Synthesis in Heat Shock Response of Saccharomyces cerevisiae

Sugiyama

Izawa

Inoue

2000

Journal of Biological Chemistry

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137

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Glutathione is synthesized in two sequential reactions catalyzed by ␥-glutamylcysteine synthetase (GSH1 gene product) and glutathione synthetase (GSH2 gene product). The expression of GSH1 in Saccharomyces cerevisiae has been known to be up-regulated by Yap1p, a critical transcription factor for the oxidative stress response in yeast. The present study demonstrates that GSH2 expression is also regulated by Yap1p under oxidative stress-induced conditions. In addition to oxidative stress, expression of GSH1 and GSH2 was induced by heat shock stress in a Yap1p-dependent manner with subsequent increases in intracellular glutathione content. Oxygen respiration rate increased when cells were exposed to higher temperatures, and as a result, intracellular oxidation levels were increased. The heat shock-induced expression of GSH1 and GSH2 did not occur under anaerobic conditions. Furthermore, even under aerobic conditions, the heat shock response of these genes was not observed when cells were pretreated with KCN to block oxygen respiration. We speculate that heat shock stress enhances oxygen respiration, which in turn results in an increase in the generation of reactive oxygen species in mitochondria. This signal may be mediated by Yap1p, resulting in the elevation of intracellular glutathione levels.Stress-inducible proteins are synthesized by all organisms, and important functional insights of this group of proteins have been obtained from studies with the heat shock protein (HSP). 1A sudden increase in the temperature at which cells are growing induces the synthesis of a set of HSPs. When the temperature of Escherichia coli cells is increased from 30 to 42°C, the intracellular concentration of sigma factor 32 increases 15-20-fold. The sigma factor is one of the components of E. coli RNA polymerase, and substitution of a vegitative sigma factor ( 70 ) by 32 modifies the RNA polymerase to specifically recognize the promoter of HSP genes. In higher eukaryotes, a heat shock transcription factor is trimerized, phosphorylated, and translocated into the nucleus by heat shock stress and binds to the heat shock element (HSE) on the promoter of HSP genes to activate transcription (for a review, see Ref.

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

The Yap1p-dependent Induction of Glutathione Synthesis in Heat Shock Response of Saccharomyces cerevisiae

Sugiyama

Izawa

Inoue

2000

Journal of Biological Chemistry

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137

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“…Thioredoxin and glutaredoxin both have thioltransferase activity that catalyzes the reduction of protein disulfide (Holmgren, 1989). They are thought to function in antioxidative defense based on the finding that knockout mutants of yeast lacking thioredoxin and glutaredoxin are sensitive to oxidative stress (Luikenhuis et al, 1998;Izawa et al, 1999). In addition, thioredoxine and glutaredoxin are electron donors for the lipid peroxide-scavenging peroxidase, peroxiredoxin (Rouhier et al, 2002).…”

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confidence: 99%

A Novel cis-Element That Is Responsive to Oxidative Stress Regulates Three Antioxidant Defense Genes in Rice

et al. 2005

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All organisms have defense systems against oxidative stress that include multiple genes of antioxidant defense. These genes are induced by reactive oxygen species under condition of oxidative stress. In this study, we found that a 28-bp motif is conserved on the promoter regions of three antioxidant defense genes in rice (Oryza sativa): cytosolic superoxide dismutase (sodCc1), cytosolic thioredoxin (trxh), and glutaredoxin (grx). We demonstrated that the 28-bp sequence acts as a cis-element responsive to oxidative stress by transient expression assay and designated it as CORE (coordinate regulatory element for antioxidant defense). The CORE was activated by methyl viologen treatment and induced a 3.1-fold increase in expression of the reporter gene, but it did not respond to hydrogen peroxide. The expressions of the sodCc1, trxh, and grx genes were coordinately induced by methyl viologen, suggesting that multiple genes involved in antioxidant defense are controlled by a common regulatory mechanism via CORE. Application of the mitogen-activated protein kinase kinase inhibitor caused the constitutive induction of the sodCc1, trxh, and grx genes and the activation of CORE without methyl viologen treatment. These results indicate that a mitogen-activated protein kinase cascade is involved in the gene regulation mediated by CORE.

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“…TXN has been demonstrated to be a central intracellular antioxidant as well as an important regulator of redox-sensitive gene expression (17)(18)(19)(20). In addition, TXN has been shown to act as an electron donor for ribonucleotide reductase, thereby providing deoxyribonucleotides for DNA synthesis and repair.…”

Section: Introductionmentioning

confidence: 99%

Protective effects of thioredoxin-mediated p53 activation in response to mild hyperthermia

Jung

Seo

2011

Oncol Rep

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Abstract. Recently, mild hyperthermia was shown to induce cell cycle arrest at the G 2 /M phase transition without leading to DNA damage. The mechanism of this regulation has not yet been elucidated, although p53 has been shown to be activated in response to mild hyperthermia. Here, we report the role of thioredoxin (TXN) in mild hyperthermia-induced cellular responses. Our data showed that the protein levels of p53 and its downstream gene, Gadd45a, which is an indicator of G 2 /M arrest, were significantly decreased in TXN siRNA-treated cells under conditions of mild hyperthermia (41˚C, 60 min) as compared to TXN wild-type cells, implying that TXN might play an important role in mild hyperthermia-induced G 2 /M arrest via p53 and Gadd45a activation. Furthermore, the release of cyclin-dependent kinase Cdc2, known to be regulated by Gadd45a under G 2 /M arrest, was inhibited from the nucleus for arrest in the G 2 /M phase in TXN downregulated cells under mild hyperthermia. We suggest that G 2 /M arrest mediated via the TXN-modulated p53 in response to mild hyperthermia may provide critical insight into the clinical use of mild hyperthermia to induce an adaptive response against genotoxic stresses.

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Thioredoxin Deficiency Causes the Constitutive Activation of Yap1, an AP-1-like Transcription Factor in Saccharomyces cerevisiae

Cited by 130 publications

References 49 publications

The Yap1p-dependent Induction of Glutathione Synthesis in Heat Shock Response of Saccharomyces cerevisiae

The Yap1p-dependent Induction of Glutathione Synthesis in Heat Shock Response of Saccharomyces cerevisiae

A Novel cis-Element That Is Responsive to Oxidative Stress Regulates Three Antioxidant Defense Genes in Rice

Protective effects of thioredoxin-mediated p53 activation in response to mild hyperthermia

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