Multiple functions of 2-Cys peroxiredoxins, I and II, and their regulations via post-translational modifications

Abstract

Peroxiredoxins (Prxs) are an unusual family of thiol-specific peroxidases that possess a binding site for H₂O₂ and rely on a conserved cysteine residue for rapid reaction with H₂O₂. Among 6 mammalian isoforms (Prx I to VI), Prx I and Prx II are mainly found in the cytosol and nucleus. Prx I and Prx II function as antioxidant enzymes and protein chaperone under oxidative distress conditions. Under oxidative eustress conditions, Prx I and Prx II regulate the levels of H₂O₂ at specific area of the cells as well as sense and transduce H₂O₂ signaling to target proteins. Prx I and Prx II are known to be covalently modified on multiple sites: Prx I is hyperoxidized on Cys⁵²; phosphorylated on Ser³², Thr⁹⁰, and Tyr¹⁹⁴; acetylated on Lys⁷, Lys¹⁶, Lys²⁷, Lys³⁵, and Lys¹⁹⁷; glutathionylated on Cys⁵², Cys⁸³, and Cys¹⁷³; and nitrosylated on Cys⁵² and Cys⁸³, whereas Prx II is hyperoxidized on Cys⁵¹; phosphorylated on Thr⁸⁹, Ser¹¹², and Thr¹⁸²; acetylated on Ala² and Lys¹⁹⁶; glutathionylated on Cys⁵¹ and Cys¹⁷²; and nitrosylated on Cys⁵¹ and Cys¹⁷². In this review, we describe how these post-translational modifications affect various functions of Prx I and Prx II.

Keywords: Acetylation; Chaperone; Glutathionylation; Hydrogen peroxide (H(2)O(2)); Intracellular messenger; Peroxidase; Peroxiredoxin; Phosphorylation; S-Nitrosylation; Thiol oxidation.