Proteasomit

Proteasomit, commonly known as the proteasome, is a large protease complex that carries out selective protein degradation in the cell as part of the ubiquitin-proteasome system. It plays a central role in regulating many cellular processes by removing damaged, misfolded, and regulatory proteins, thereby controlling cell cycle progression, signaling, and stress responses. The proteasome also contributes to the generation of peptide fragments presented by MHC class I molecules, linking protein turnover to immune surveillance.

The most common form in eukaryotic cells is the 26S proteasome, consisting of a central 20S core particle capped by one or two 19S regulatory particles. The 20S core is a cylindrical structure formed from four stacked rings of seven subunits (α7-β7-β7-α7). The inner chamber houses the proteolytic active sites. The 19S caps recognize polyubiquitin chains on substrates, unfold them using ATP-dependent helicases, remove ubiquitin, and translocate the unfolded protein into the core for degradation.

Within the 20S core, proteolysis is carried out by three main catalytic activities attributed to specific β subunits: a caspase-like activity (β1), a trypsin-like activity (β2), and a chymotrypsin-like activity (β5). The combined action of these proteolytic sites generates small peptide fragments from protein substrates.

Regulation of proteasome activity involves assembly with regulatory particles, post-translational modifications, and interaction with activators such as PA28 or PA200 in specialized contexts. The proteasome is essential for cellular homeostasis; its dysfunction is associated with diseases including neurodegenerative disorders and cancer. Proteasome inhibitors, such as bortezomib and carfilzomib, are used clinically to disrupt proteasome function in certain cancers.