Proteasomal defense of oxidative protein modifications.

The proteasome has an important role in the degradation of normal, damaged, mutant, or misfolded proteins. This includes the degradation of normal and regulatory proteins in the cellular metabolism and additionally the removal of damaged proteins as a stress response. The two well-described proteasome regulators, the 11S and the 19S regulators, forming together with the 20S 'core' proteasome various forms of the proteasome, including the ATP-stimulated 26S proteasome. As a result of aerobic metabolism, reactive oxygen species (ROS) are constantly generated during the lifetime of biological organisms. Consequently a permanent generation of oxidative damage takes place. This includes the formation of oxidatively modified proteins. These oxidized protein derivatives tend to aggregate, and accumulation of these aggregates may lead to cell death. To prevent this, such oxidatively modified proteins are selectively recognized and either repaired or degraded by the proteasome. The current knowledge of the repair systems and the degradation mechanism is reviewed here. The possible interactions between the ubiquitin-proteasome-system, the chaperone system, the protein repair mechanisms, and other antioxidative defense strategies are highlighted.