title: Controlled elimination of intracellular H(2)O(2): regulation of peroxiredoxin, catalase, and glutathione peroxidase via post-translational modification.
abstract: The predominant enzymes responsible for elimination of hydrogen peroxide (H(2)O(2)) in cells are peroxiredoxins (Prxs), catalase, and glutathione peroxidases (GPxs). Evidence suggests that catalytic activities of certain isoforms of these H(2)O(2)-eliminating enzymes are extensively regulated via posttranslational modification. Prx I and Prx II become inactivated when phosphorylated on Thr(90) by cyclin B-dependent kinase Cdc2. In addition, the active-site cysteine of Prx I-IV undergoes a reversible sulfinylation (oxidation to cysteine sulfinic acid) in cells. Desulfinylation (reduction to cysteine) is achieved by a novel enzyme named sulfiredoxin. c-Abl and Arg nonreceptor protein tyrosine kinases associate with catalase in cells treated with H(2)O(2) by mechanisms involving the SH3 domains of the kinases and the Pro(293)PheAsnPro motif of catalase and activate catalase by phosphorylating it on Tyr(231) and Tyr(386). Similarily, GPx1 is activated by c-Abl- and Arg-mediated phosphorylation. The tyrosine phosphorylation is critical for ubiquitination-dependent degradation of catalase.
authors.affiliation: Laboratory of Cell Signaling, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA. sgrhee@nih.gov
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.forename: Kap-Seok
authors.initials: KS
authors.lastname: Yang
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Kang
authors.forename: Hyun Ae
authors.initials: HA
authors.lastname: Woo
authors.forename: Tong-Shin
authors.initials: TS
authors.lastname: Chang
mesh_terms: D000818:Animals; D002374:Catalase / Q000378:metabolism*; D005786:Gene Expression Regulation; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D054464:Peroxiredoxins; D011499:Protein Processing, Post-Translational
chemical_list: D006861:Hydrogen Peroxide; D010544:Peroxidases; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase