TY - JOUR

T1 - Redox control of the ubiquitin-proteasome system

T2 - from molecular mechanisms to functional significance

AU - Kriegenburg, Franziska

AU - Poulsen, Esben G

AU - Koch, Annett

AU - Krüger, Elke

AU - Hartmann-Petersen, Rasmus

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Oxidation-Reduction

KW - Oxidative Stress

KW - Proteasome Endopeptidase Complex

KW - Proteins

KW - Ubiquitin

U2 - 10.1089/ars.2010.3590

DO - 10.1089/ars.2010.3590

M3 - Journal article

C2 - 21314436

VL - 15

SP - 2265

EP - 2299

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 8

ER -