title: An ubiquitin ligase recognizing a protein oxidized by iron: implications for the turnover of oxidatively damaged proteins.
abstract: Protein oxidation is a natural consequence of aerobic metabolism in cells. Oxidative modification of amino acid residues of proteins causes to lose activity or function of proteins. Organisms have thus developed pathways to remove oxidized proteins by rapid protein degradation. These pathways are important components in cellular quality control mechanisms. It has been suggested that oxidized proteins are degraded by the proteasome. However, whether ubiquitylation is necessary for the degradation of oxidized proteins remains a controversial issue. We have recently identified HOIL-1 (heme-oxidized IRP2 ubiquitin ligase-1) as an E3 ligase that recognizes a protein that has been oxidized by iron. This review describes the recent progress made in understanding the ubiquitin-proteolytic pathway and the regulation of iron metabolism. The process involved in eliminating oxidized proteins and the possible roles that HOIL-1 ubiquitin ligase may play in these processes are discussed.
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, and CREST, JST, Kawaguchi, Saitama 332-0012. kiwai@med.osaka-cu.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism; D006418:Heme / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D035925:Iron-Regulatory Proteins / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D035925:Iron-Regulatory Proteins; D009097:Multienzyme Complexes; D016601:RNA-Binding Proteins; D025801:Ubiquitin; D006418:Heme; D007501:Iron; D044767:Ubiquitin-Protein Ligases; D003546:Cysteine Endopeptidases