title: A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation.
abstract: The Yap1 transcription factor regulates hydroperoxide homeostasis in S. cerevisiae. Yap1 is activated by oxidation when hydroperoxide levels increase. We show that Yap1 is not directly oxidized by hydroperoxide. We identified the glutathione peroxidase (GPx)-like enzyme Gpx3 as a second component of the pathway, serving the role of sensor and transducer of the hydroperoxide signal to Yap1. When oxidized by H2O2, Gpx3 Cys36 bridges Yap1 Cys598 by a disulfide bond. This intermolecular disulfide bond is then resolved into a Yap1 intramolecular disulfide bond, the activated form of the regulator. Thioredoxin turns off the pathway by reducing both sensor and regulator. These data reveal a redox-signaling function for a GPx-like enzyme and elucidate a eukaryotic hydroperoxide-sensing mechanism. Gpx3 is thus a hydroperoxide receptor and redox-transducer.
authors.affiliation: Laboratoire Stress Oxydants et Cancers, SBGM, DBJC, CEA-Saclay, 91191 Gif-sur-Yvette, Cedex, France.
authors.forename: Agnès
authors.initials: A
authors.lastname: Delaunay
authors.forename: Delphine
authors.initials: D
authors.lastname: Pflieger
authors.forename: Marie Bénédicte
authors.initials: MB
authors.lastname: Barrault
authors.forename: Joelle
authors.initials: J
authors.lastname: Vinh
authors.forename: Michel B
authors.initials: MB
authors.lastname: Toledano
mesh_terms: D001483:Base Sequence; D003545:Cysteine; D004271:DNA, Fungal; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004220:Disulfides; D005656:Fungal Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005978:Glutathione / Q000235:genetics / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013879:Thioredoxins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; D004220:Disulfides; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D005978:Glutathione; D003545:Cysteine