20S Proteasome (20S)

The 20S proteasome is a large, barrel-shaped multi-catalytic protease complex that serves as the core particle of the eukaryotic and archaeal proteasome system. It is essential for regulated protein degradation in cells, maintaining protein homeostasis by removing misfolded, damaged, or regulatory proteins through an ATP- and ubiquitin-independent mechanism. It is composed of four stacked heptameric rings: two outer α-rings and two inner β-rings. The β-subunits contain three main catalytic sites: β1 (caspase-like), β2 (trypsin-like), and β5 (chymotrypsin-like). Dysregulation contributes to diseases such as cancer and neurodegenerative disorders. Several clinically used drugs inhibit its chymotrypsin-like site to induce apoptosis in cancer cells.

Inhibition of chymotrypsin-like activity (β5), trypsin-like activity (β2), and caspase-like activity (β1) leads to accumulation of misfolded proteins and induction of apoptosis.