proteasoom

Proteasoom is a large protease complex responsible for degrading intracellular proteins that have been marked for destruction by the ubiquitin–proteasome system. In eukaryotic cells the principal degradative form is the 26S proteasoom, composed of a 20S core particle capped by one or two 19S regulatory particles. The core particle consists of four stacked rings (two outer alpha rings and two inner beta rings); the beta subunits carry the proteolytic active sites, while the alpha rings help gate substrate entry.

Mechanism and function: The system tags damaged, misfolded, or short‑lived proteins with polyubiquitin chains. The 19S regulatory particle recognizes these tags, unfolds the substrate, and uses ATP to translocate it into the 20S core, where proteolysis occurs. The core provides three principal proteolytic activities: chymotrypsin‑like, trypsin‑like, and caspase‑like. This coordinated activity maintains protein homeostasis, regulates numerous cellular processes, and allows generation of peptide fragments for immune presentation.

Cellular roles and regulation: The proteasoom influences cell cycle progression, transcription, DNA repair, and signal transduction by controlling the abundance of regulatory proteins. It also contributes to antigen processing for MHC class I presentation. Proteasome activity is subject to regulation by post‑translational modifications, interacting partners, and cellular stress, and impaired function can lead to accumulation of damaged proteins and disease.

Clinical relevance: Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib are used clinically to treat certain hematologic cancers, notably multiple myeloma, by disrupting proteostasis and promoting cancer cell death. Beyond oncology, the proteasoom remains a focus of research in neurodegenerative diseases and aging, where its modulation may influence protein aggregation and immune signaling.

History: The ubiquitin–proteasome system was established in the late 20th century, with key contributions from Hershko, Ciechanover, and Rose. Subsequent work delineated the architecture and subunit organization of the 26S proteasoom.