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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

Authors

  • Budanov AV
  • Sablina AA
  • Feinstein E
  • Koonin EV
  • Chumakov PM

Journal

Science (New York, N.Y.)

Publication Data

April 23, 2004

Associated Grants

None

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