A Thiol Peroxidase Is an H2O2 Receptor and Redox-Transducer in Gene Activation

Delaunay, A; Pflieger, Delphine; Barrault, Marie Bénédicte; Vinh, Joëlle; Toledano, Michel B.

doi:10.1016/s0092-8674(02)01048-6

Cited by 812 publications

(804 citation statements)

References 31 publications

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“…In Escherichia coli, the mechanism by which HP exposure causes induction of the HP regulon is through the formation of an intramolecular disulfide bond within the product of the oxyR gene, which converts it to a transcriptional activator (Zheng et al, 1998). In yeast, the transcriptional regulator Yap1p is modified by the glutathione peroxidase-like enzyme Gpx3p in response to HP exposure (Delaunay et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Shapira

Segal

Botstein

2004

MBoC

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The effects of oxidative stress on yeast cell cycle depend on the stress-exerting agent. We studied the effects of two oxidative stress agents, hydrogen peroxide (HP) and the superoxide-generating agent menadione (MD). We found that two small coexpressed groups of genes regulated by the Mcm1-Fkh2-Ndd1 transcription regulatory complex are sufficient to account for the difference in the effects of HP and MD on the progress of the cell cycle, namely, G1 arrest with MD and an S phase delay followed by a G2/M arrest with HP. Support for this hypothesis is provided by fkh1fkh2 double mutants, which are affected by MD as we find HP affects wild-type cells. The apparent involvement of a forkhead protein in HP-induced cell cycle arrest, similar to that reported for Caenorhabditis elegans and human, describes a potentially novel stress response pathway in yeast. INTRODUCTIONReactive oxygen species (ROS) are by-products of aerobic metabolism, but are also attributes of the extracellular environment. They pose a threat to organisms by damaging a variety of cellular macromolecules, including DNA, membrane lipids, and proteins and are implicated with carcinogenesis, aging, and numerous degenerative diseases (Finkel and Holbrook, 2000;Neumann et al., 2003). The major ROS derived from oxygen are superoxide ions, hydrogen peroxide (HP), and hydroxy radicals, ordered here by increasing reactivity (reviewed in Shackelford et al., 2000).Oxidative stress in yeast has been studied by exposing cells to agents that are already reactive, typically HP, or drugs that cause the intracellular accumulation of reactive oxygen species (Godon et al., 1998;Dumond et al., 2000;Gasch et al., 2000). Menadione (MD) is such a drug, generating reactive superoxide ions, which can be further oxidized to give HP (Monks et al., 1992;Shackelford et al., 2000). It has been previously reported that exposure to HP or MD results in a cell cycle arrest (Flattery-O'Brien and Dawes, 1998;Leroy et al., 2001). However, the arrest points are not similar for the two agents. MD was reported to arrest cells at the G1 phase of the cell cycle, whereas HP was suggested to cause a G2 arrest by an alternate mechanism from that affected by MD (Flattery-O'Brien and Dawes, 1998); others reported that HP exposure causes a delay in the S phase (Leroy et al., 2001).Hundreds of genes are regulated so that they are expressed at specific times in the cell cycle and not at others (Cho et al., 1998;Spellman et al., 1998). The major part of this coordination is achieved by the sequential activation of a small number of transcription regulators (reviewed in Mendenhall and Hodge, 1998): MBF (a complex of Mbp1p and Swi6p) and SBF (a complex of Swi4p and Swi6p) are responsible for activating G1 transcription (Koch et al., 1993); Fkh1p and a complex formed by the cooperative promoter binding of Mcm1p and Fkh2p and a later recruitment of Ndd1p are responsible for activating G2/M transcription (Koranda et al., 2000;Kumar et al., 2000;Pic et al., 2000;Hollenhorst et al., 2001); Swi5p and Ace2p...

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Section: Discussionmentioning

confidence: 99%

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Shapira

Segal

Botstein

2004

MBoC

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“…Intriguingly, redox control of Yap1 is not exerted through oxidation of Yap1 itself, but via glutathione peroxidase (Gpx)-like enzyme, Gpx3, which acts as the sensor and tranducer of the redox signals. Oxidation of cysteine 36 of Gpx3 resulted in an intermolecular disulfide bond with cysteine 598 of Yap-1, and the resolution of this intermolecular disulfide bond into a Yap1 intramolecular disulfide bond, causes activation of the regulator [187].…”

Section: Redox Control Through Functional Dimerization Of Redox Enzymmentioning

confidence: 99%

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Janssen–Heininger¹,

Mossman²,

Heintz³

et al. 2008

Free Radical Biology and Medicine

698

652

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“…Txn1 is also required for DNA-binding activity of the transcription factors NFκB, AP1, steroid hormone receptors, and p53 [1,[28][29][30]. In yeast exposed to oxidants, dithiol-disulfide exchange reactions between Txn, glutathione peroxidase, and the AP-1 family transcription factor YAP1, results in oxidative activation of YAP1 and induction of downstream genes [31].…”

Section: Introductionmentioning

confidence: 99%

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

Bondareva¹,

Capecchi²,

Iverson³

et al. 2007

Free Radical Biology and Medicine

102

115

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Thioredoxin reductases (Txnrd)1 maintain intracellular redox homeostasis in most organisms. Metazoans Txnrds also participate in signal transduction. Mouse embryos homozygous for a targeted null mutation of the txnrd1 gene, encoding the cytosolic thioredoxin reductase, were viable at embryonic day 8.5 (E8.5) but not at E9.5. Histology revealed that txnrd1 −/− cells were capable of proliferation and differentiation; however, mutant embryos were smaller than wild-type littermates and failed to gastrulate. In situ marker gene analyses indicated primitive streak mesoderm did not form. Microarray analyses on E7.5 txnrd −/− and txnrd +/+ littermates showed similar mRNA levels for peroxiredoxins, glutathione reductases, mitochondrial Txnrd2, and most markers of cell proliferation. Conversely, mRNAs encoding sulfiredoxin, IGF-binding protein 1, carbonyl reductase 3, glutamate cysteine ligase, glutathione S-transferases, and metallothioneins were more abundant in mutants. Many gene expression responses mirrored those in thioredoxin reductase 1-null yeast; however mice exhibited a novel response within the peroxiredoxin catalytic cycle. Thus, whereas yeast induce peroxiredoxin mRNAs in response to thioredoxin reductase disruption, mice induced sulfiredoxin mRNA. In summary, Txnrd1 was required for correct patterning of the early embryo and progression to later development. Conserved responses to Txnrd1 disruption likely allowed proliferation and limited differentiation of the mutant embryo cells.

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A Thiol Peroxidase Is an H2O2 Receptor and Redox-Transducer in Gene Activation

Cited by 812 publications

References 31 publications

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Disruption of Yeast Forkhead-associated Cell Cycle Transcription by Oxidative Stress

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

Effects of thioredoxin reductase-1 deletion on embryogenesis and transcriptome

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