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 H 2 O 2 and rely on a conserved cysteine residue for rapid reaction with H 2 O 2 . 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 H 2 O 2 at specific area of the cells as well as sense and transduce H 2 O 2 signaling to target proteins. Prx I and Prx II are known to be covalently modified on multiple sites: Prx I is hyperoxidized on Cys 52 ; phosphorylated on Ser 32 , Thr 90 , and Tyr 194 ; acetylated on Lys 7 , Lys 16 , Lys 27 , Lys 35 , and Lys 197 ; glutathionylated on Cys 52 , Cys 83 , and Cys 173 ; and nitrosylated on Cys 52 and Cys 83 , whereas Prx II is hyperoxidized on Cys 51 ; phosphorylated on Thr 89 , Ser 112 , and Thr 182 ; acetylated on Ala 2 and Lys 196 ; glutathionylated on Cys 51 and Cys 172 ; and nitrosylated on Cys 51 and Cys 172 . In this review, we describe how these post -translational mod- ifications affect various functions of Prx I and Prx II.