Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD.
Acting as a signal, hydrogen peroxide circumvents antioxidant defense by overoxidizing peroxiredoxins (Prxs), the enzymes that metabolize peroxides. We show that sestrins, a family of proteins whose expression is modulated by p53, are required for regeneration of Prxs containing Cys-SO(2)H, thus reestablishing the antioxidant firewall. Sestrins contain a predicted redox-active ... domain homologous to AhpD, the enzyme catalyzing the reduction of a bacterial Prx, AhpC. Purified Hi95 (sestrin 2) protein supports adenosine triphosphate-dependent reduction of overoxidized PrxI in vitro, indicating that unlike AhpD, which is a disulfide reductase, sestrins are cysteine sulfinyl reductases. As modulators of peroxide signaling and antioxidant defense, sestrins constitute potential therapeutic targets.
Mesh Terms:
Amino Acid Sequence, Amino Acid Substitution, Cell Division, Cell Line, Tumor, Cell Survival, Cells, Cultured, Heat-Shock Proteins, Humans, Hydrogen Peroxide, Molecular Sequence Data, Mutation, Nuclear Proteins, Oxidation-Reduction, Oxidoreductases, Peroxidases, Peroxiredoxins, RNA, Small Interfering, Reactive Oxygen Species, Recombinant Proteins, Tumor Suppressor Protein p53
Amino Acid Sequence, Amino Acid Substitution, Cell Division, Cell Line, Tumor, Cell Survival, Cells, Cultured, Heat-Shock Proteins, Humans, Hydrogen Peroxide, Molecular Sequence Data, Mutation, Nuclear Proteins, Oxidation-Reduction, Oxidoreductases, Peroxidases, Peroxiredoxins, RNA, Small Interfering, Reactive Oxygen Species, Recombinant Proteins, Tumor Suppressor Protein p53
Science
Date: Apr. 23, 2004
PubMed ID: 15105503
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