ubiquitinációjának

Ubiquitination is a post‑translational modification in which the small protein ubiquitin is covalently attached to target proteins. This process marks proteins for various cellular fates, such as proteasomal degradation, altered subcellular localization, or changes in activity. The reaction is catalyzed sequentially by three main classes of enzymes. First, an E1 activating enzyme uses ATP to adenylate the C‑terminal glycine of ubiquitin, then forms a thioester bond with a cysteine residue on the enzyme. Next, an E2 conjugating enzyme receives ubiquitin from the E1 and presents it to the target protein. Finally, an E3 ligase recognizes a specific substrate and facilitates the transfer of ubiquitin to a lysine residue (or the N‑terminus) on that substrate. Different E3 ligases confer substrate specificity, and some E2–E3 combinations preferentially create distinct ubiquitin chain linkages, notably Lys48‑linked chains for degradation and Lys63‑linked chains for signaling.

Ubiquitination is reversible; deubiquitinating enzymes (DUBs) remove ubiquitin to regulate protein turnover and signal strength. Dysregulation of ubiquitination pathways is implicated in neurodegenerative diseases, cancer, immune disorders, and viral pathogenesis. In therapeutic contexts, modulation of the ubiquitin–proteasome system—such as proteasome inhibitors used in multiple myeloma—exploits the centrality of ubiquitination in cell homeostasis. The study of ubiquitination continues to reveal intricate layers of regulation in cellular physiology and pathology.