Ubiquitin-proteasome system
DEUbiquitin-Proteasom-System
The ubiquitin-proteasome system (UPS) is a major route for selective degradation of short-lived, misfolded, or regulatory proteins, complementary to autophagy-lysosomal degradation. Target proteins are tagged with ubiquitin chains via E1 activating, E2 conjugating, and E3 ligase enzymes, with the E3 ligase providing substrate specificity; K48-linked polyubiquitin chains are the canonical proteasome-targeting signal, while other linkages have non-degradative roles. Tagged proteins are then unfolded and degraded into short peptides inside the 26S proteasome. UPS activity declines with age, contributing to loss of proteostasis and neurodegeneration.
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Sources
- Wilkinson KD. (2005). The discovery of ubiquitin-dependent proteolysis. *Proceedings of the National Academy of Sciences USA*doi:10.1073/pnas.0504842102
- Löw P. (2015). The amazing ubiquitin-proteasome system: structural components and implication in aging. *International Review of Cell and Molecular Biology*doi:10.1016/bs.ircmb.2014.09.002