Proteasomissa

Proteasomissa is a term used to describe processes and activities that take place within the proteasome, a large proteolytic complex central to cellular protein turnover. In eukaryotic cells, the proteasome degrades unwanted or damaged proteins as part of the ubiquitin-proteasome system, helping to regulate many cellular functions and maintain protein homeostasis.

The proteasome exists mainly as a two-part assembly: a cylindrical 20S core particle that performs proteolysis and regulatory particles, typically the 19S caps, that recognize, unfold, and feed substrates into the core. In its most common form, the full complex is the 26S proteasome, which requires ATP to unfold substrates tagged with polyubiquitin chains. The proteolytic chamber houses multiple active sites with different specificities, providing chymotrypsin-like, trypsin-like, and caspase-like activities. Deubiquitinating enzymes associated with the regulatory particles remove ubiquitin before substrate translocation.

Proteasomal activity influences numerous cellular processes, including cell cycle progression, gene expression, and stress responses. It also plays a key role in antigen presentation, as peptide fragments generated by the proteasome are loaded onto MHC class I molecules for immune surveillance. Immunoproteasomes, alternative catalytic subunits induced by inflammatory cytokines, can alter peptide production to optimize immune recognition.

Clinical relevance is highlighted by therapies targeting the proteasome. Proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib are used in the treatment of certain cancers, notably multiple myeloma, by disrupting protein turnover and inducing cancer cell death. Resistance and side effects remain areas of ongoing research in proteasome-targeted therapies.