ubiquitinproteaszomális

The ubiquitin-proteasome system (UPS) is the principal pathway for regulated intracellular protein degradation in eukaryotic cells. It controls protein turnover, quality control, and the regulation of many cellular processes by eliminating unwanted or damaged proteins.

Ubiquitination, the tagging of substrates with ubiquitin, is carried out by a cascade of enzymes: an E1 ubiquitin-activating enzyme activates ubiquitin, an E2 conjugating enzyme transfers it, and an E3 ubiquitin ligase confers substrate specificity by attaching ubiquitin to target proteins. Proteins can receive a single ubiquitin or form polyubiquitin chains. The type of linkage and the length of the chain determine the fate of the substrate; for example, K48-linked polyubiquitin chains typically target proteins for degradation by the proteasome, while other linkages can regulate localization, signaling, or DNA repair.

The 26S proteasome degrades polyubiquitinated substrates. It consists of a catalytic 20S core particle and one or two 19S regulatory particles that recognize ubiquitin chains, unfold substrates, and channel them into the core for proteolysis into short peptides. Deubiquitinating enzymes may remove ubiquitin moieties to recycle ubiquitin and modulate degradation timing.

The UPS is essential for numerous physiological processes, including cell cycle control, development, immune surveillance, and response to stress. Its dysregulation is associated with diseases such as cancer and neurodegenerative disorders. Therapeutic proteasome inhibitors, like bortezomib, are used clinically to treat certain malignancies, illustrating the system’s importance in health and disease.