The proteasome is part of the main mechanism by which cells regulate specific protein concentration and degrade misfolded proteins. Specifically, ubiquitin is a key molecule known to cooperate with proteasome. Besides, its polymerization acts as a degradation signal of many target proteins. Moreover, ubiquitin proteasome system (UPS) controls almost all basic cellular processes by degrading short-lived regulatory proteins or structurally abnormal proteins. Such as cell cycle progression, signal transduction, cell death, immune response, metabolism, protein quality control, and development.


Furthermore, 20S CP (alias 20S proteasome) has good structural characteristics. It is a well-organized protein complex with a sedimentation coefficient of 20S. Meanwhile, 20S core particle proteasome plays an important role in cell function by degrading protein substrates that are no longer needed or damaged. Up to 20% of all cellular proteins are substrates of 20S CP proteasome, and gated residues play a key role in controlling protein hydrolysis. Nonetheless, proteasome plays a key role in regulating cell homeostasis by degrading target protein substrates. Today, we will introduce a selective 20S proteasome inhibitor, Lactacystin.

Lactacystin, an Antibiotic, is a Selective 20S Proteasome Inhibitor.

First of all, Lactacystin is an antibiotic Streptomyces spp. Metabolite. Importantly, Lactacystin is a potent and selective proteasome inhibitor with an IC50 of 4.8 μM for 20S proteasome.

In the second place, Lactacystin also inhibits the lysosomal enzyme cathepsin A. Particularly, Lactacystin inhibits cell growth and induces neurite outgrowth. Obviously, Lactacystin with microinjection of 2 µg induces a Parkinson’s disease-like motor phenotype 5-7 days after injection in young and adult mice.

All in all, Lactacystin, an antibiotic, is a selective 20S proteasome inhibitor.


Savolainen MH, et al. Exp Brain Res. 2017 Jul;235(7):2189-2202.