Regeneration of Peroxiredoxins by p53-Regulated Sestrins, Homologs of Bacterial AhpD
Engelhardt Institute of Molecular Biology · National Institutes of Health · +4 more institutions
Abstract
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…
Citation impact
- FWCI
- 15.07
- Percentile
- 100%
- References
- 29
Authors
5- AVAndrei V. BudanovCorresponding
Engelhardt Institute of Molecular Biology, National Institutes of Health, Cleveland Clinic, Quark Pharmaceuticals (United States), Russian Cancer Research Center NN Blokhin, National Center for Biotechnology Information
- ASAnna SablinaCorresponding
Engelhardt Institute of Molecular Biology, National Institutes of Health, Cleveland Clinic, Quark Pharmaceuticals (United States), Russian Cancer Research Center NN Blokhin, National Center for Biotechnology Information
- EFElena Feinstein
Engelhardt Institute of Molecular Biology, National Institutes of Health, Cleveland Clinic, Quark Pharmaceuticals (United States), Russian Cancer Research Center NN Blokhin, National Center for Biotechnology Information
- EVEugene V. Koonin
Engelhardt Institute of Molecular Biology, National Institutes of Health, Cleveland Clinic, Quark Pharmaceuticals (United States), Russian Cancer Research Center NN Blokhin, National Center for Biotechnology Information
- PMPeter M. ChumakovCorresponding
Engelhardt Institute of Molecular Biology, National Institutes of Health, Cleveland Clinic, Quark Pharmaceuticals (United States), Russian Cancer Research Center NN Blokhin, National Center for Biotechnology Information
Topics & keywords
- Hydrogen peroxide
- Cysteine
- Antioxidant
- Biochemistry
- Chemistry
- Enzyme
- Cell biology
- Protein superfamily