Proteasomun

Proteasomun is a large protease complex responsible for the selective degradation of most intracellular proteins that have been marked for destruction by the small protein ubiquitin. It is a central component of the ubiquitin-proteasome system, which regulates protein turnover, quality control, and various cellular processes such as cell cycle progression, DNA repair, and signaling.

The proteasomun consists of a cylindrical core particle, the 20S protease, and one or two regulatory caps, the 19S particles, forming the 26S proteasome in its active form. The 20S core is built from four stacked rings of seven subunits, creating a proteolytic chamber with three catalytic activities: beta1 (caspase-like), beta2 (trypsin-like), and beta5 (chymotrypsin-like). The 19S regulatory particle recognizes polyubiquitinated substrates, unfolds them, and feeds them into the core in an ATP-dependent manner. The proteasome thus couples recognition of ubiquitinated proteins with regulated proteolysis.

In immune cells, an inducible form called the immunoproteasome replaces certain catalytic subunits and enhances the generation of antigenic peptides presented on MHC class I molecules. Thymoproteasomes, another variant, contribute to T cell development in the thymus. Beyond antigen presentation, the proteasomun participates in quality control by removing misfolded or damaged proteins and modulating levels of regulatory proteins involved in signaling pathways.

Inhibitors of the proteasomun, such as bortezomib and carfilzomib, are used clinically to treat certain cancers. Dysregulation of proteasomal activity has been linked to neurodegenerative diseases and other conditions. Note that the standard term is proteasome; proteasomun may reflect alternate spellings or language usage.