title: Thiol peroxidases mediate specific genome-wide regulation of gene expression in response to hydrogen peroxide.
abstract: Hydrogen peroxide is thought to regulate cellular processes by direct oxidation of numerous cellular proteins, whereas antioxidants, most notably thiol peroxidases, are thought to reduce peroxides and inhibit H(2)O(2) response. However, thiol peroxidases have also been implicated in activation of transcription factors and signaling. It remains unclear if these enzymes stimulate or inhibit redox regulation and whether this regulation is widespread or limited to a few cellular components. Herein, we found that Saccharomyces cerevisiae cells lacking all eight thiol peroxidases were viable and withstood redox stresses. They transcriptionally responded to various redox treatments, but were unable to activate and repress gene expression in response to H(2)O(2). Further studies involving redox transcription factors suggested that thiol peroxidases are major regulators of global gene expression in response to H(2)O(2). The data suggest that thiol peroxidases sense and transfer oxidative signals to the signaling proteins and regulate transcription, whereas a direct interaction between H(2)O(2) and other cellular proteins plays a secondary role.
authors.affiliation: Department of Biochemistry, University of Nebraska, Lincoln, NE 68588-0664, USA.
authors.forename: Dmitri E
authors.initials: DE
authors.lastname: Fomenko
authors.forename: Ahmet
authors.initials: A
authors.lastname: Koc
authors.forename: Natalia
authors.initials: N
authors.lastname: Agisheva
authors.forename: Michael
authors.initials: M
authors.lastname: Jacobsen
authors.forename: Alaattin
authors.initials: A
authors.lastname: Kaya
authors.forename: Mikalai
authors.initials: M
authors.lastname: Malinouski
authors.forename: Julian C
authors.initials: JC
authors.lastname: Rutherford
authors.forename: Kam-Leung
authors.initials: KL
authors.lastname: Siu
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Jin
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Winge
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D001483:Base Sequence; D005786:Gene Expression Regulation / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000235:genetics; D010544:Peroxidases / Q000172:deficiency / Q000378:metabolism*; D010641:Phenotype; D012269:Ribosomal Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
chemical_list: D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins; D006861:Hydrogen Peroxide; D010544:Peroxidases; C496254:Tsa2 protein, S cerevisiae