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.
Pubmed ID: 15105503 RIS Download
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