Regeneration of peroxiredoxins by p53-regulated sestrins, homologs of bacterial AhpD
AV Budanov, AA Sablina, E Feinstein, EV Koonin… - Science, 2004 - science.org
AV Budanov, AA Sablina, E Feinstein, EV Koonin, PM Chumakov
Science, 2004•science.orgActing 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-SO2H, 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 …
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-SO2H, 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 …
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-SO2H, 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.
AAAS