title: Redox control of the ubiquitin-proteasome system: from molecular mechanisms to functional significance.
abstract: In their natural environments, cells are regularly exposed to oxidizing conditions that may lead to protein misfolding. If such misfolded proteins are allowed to linger, they may form insoluble aggregates and pose a serious threat to the cell. Accumulation of misfolded, oxidatively damaged proteins is characteristic of many diseases and during aging. To counter the adverse effects of oxidative stress, cells can initiate an antioxidative response in an attempt to repair the damage, or rapidly channel the damaged proteins for degradation by the ubiquitin-proteasome system (UPS). Recent studies have shown that elements of the oxidative stress response and the UPS are linked on many levels. To manage the extra burden of misfolded proteins, the UPS is induced by oxidative stress, and special proteasome subtypes protect cells against oxidative damage. In addition, the proteasome is directly associated with a thioredoxin and other cofactors that may adjust the particle's response during an oxidative challenge. Here, we give an overview of the UPS and a detailed description of the degradation of oxidized proteins and of the crosstalk between oxidative stress and protein degradation in health and disease.
authors.affiliation: Department of Biology, University of Copenhagen, Ole Maaløes Vej 5,Copenhagen, Denmark.
authors.forename: Franziska
authors.initials: F
authors.lastname: Kriegenburg
authors.forename: Esben G
authors.initials: EG
authors.lastname: Poulsen
authors.forename: Annett
authors.initials: A
authors.lastname: Koch
authors.forename: Elke
authors.initials: E
authors.lastname: Krüger
authors.forename: Rasmus
authors.initials: R
authors.lastname: Hartmann-Petersen
mesh_terms: D000818:Animals; D006801:Humans; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex