proteasomu

Proteasome is a large protease complex that degrades many intracellular proteins that are damaged, misfolded, or no longer needed. It forms a central component of the ubiquitin–proteasome system (UPS), which marks substrates with ubiquitin chains and directs them to the proteasome for destruction. The UPS is essential for regulated protein turnover, cell cycle control, DNA repair, signal transduction, and responses to stress.

The 26S proteasome consists of two main parts: the 20S core particle and one or two 19S regulatory particles. The 20S core is a cylindrical structure built from four stacked rings (two outer α rings and two inner β rings); the proteolytic active sites reside in selected β subunits. Access to the catalytic chamber is controlled by the gating action of the α rings. The 19S regulator recognizes polyubiquitinated substrates, removes ubiquitin tags, unfolds substrates using ATPase activity, and feeds them into the core for degradation. In addition to the 19S regulator, there are alternative regulators such as PA28 (11S) and PA200 that modulate substrate specificity and processing.

Beyond quality control, the proteasome contributes to antigen processing for MHC class I presentation, generating short peptides that are loaded onto MHC molecules. It also participates in ER-associated degradation and various signaling pathways. Dysfunction or dysregulation of the proteasome is linked to aging and diseases, including neurodegenerative disorders and cancer. Proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, are used in cancer therapy, illustrating the clinical relevance of proteasome function. The ubiquitin–proteasome system was recognized with a Nobel Prize in 2004 for its foundational role in cellular regulation.