# Ubiquitin-proteasome system

The ubiquitin-proteasome system (UPS) is one of your cells' main ways to destroy proteins on purpose. It targets short-lived, misfolded, or regulatory proteins, and it complements the autophagy-lysosome route. First, a protein gets tagged with chains of a marker called ubiquitin. That tagging takes three enzyme steps (E1 activating, E2 conjugating, E3 ligase), and the E3 ligase picks the specific target. A particular chain type (K48-linked) is the classic 'destroy me' signal; other chain types do non-destructive jobs. The tagged protein is then unfolded and chopped into short peptides inside a barrel-shaped machine, the 26S proteasome. UPS activity falls with age. That contributes to the loss of protein balance and to neurodegeneration.

## Sources

- Wilkinson KD. (2005). The discovery of ubiquitin-dependent proteolysis. Proceedings of the National Academy of Sciences USA. https://doi.org/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. https://doi.org/10.1016/bs.ircmb.2014.09.002

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