proteasomal

Proteasomal is an adjective relating to the proteasome, a large protein complex responsible for controlled intracellular degradation of proteins. In eukaryotic cells, the primary system for tagging proteins for destruction is the ubiquitin-proteasome system. Target proteins are covalently linked to ubiquitin, recognized by the 19S regulatory particle, unfolded, and threaded into the proteolytic core, the 20S core particle, where proteolysis occurs. The canonical 26S proteasome consists of the 20S core particle capped on one or both ends by 19S regulatory particles. The 20S core is a cylinder with four stacked rings of seven subunits, harboring three proteolytic activities: chymotrypsin-like, trypsin-like, and caspase-like, located in the β-subunits. Activation and substrate processing require ATP hydrolysis by the 19S regulatory particle. In addition to the constitutive proteasome, inducible forms exist, such as the immunoproteasome and thymoproteasome, which replace certain β-subunits and alter cleavage preferences, affecting antigen presentation on MHC class I molecules.

Proteasomal function is essential for protein quality control, cell-cycle regulation, signaling, and stress responses. Dysregulation is linked to aging and neurodegenerative diseases; accumulation of damaged proteins can occur when proteasomal activity diminishes. The proteasome is a validated drug target; proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib are used in cancer therapy, exploiting tumor cell sensitivity to proteotoxic stress. Research on proteasomal regulation continues to illuminate how cells maintain proteostasis and how its dysfunction contributes to disease.