ubiquitylaation

Ubiquitylation is a post-translational modification in which a small protein called ubiquitin is covalently attached to a substrate protein. This process is catalyzed by a cascade of enzymes, typically involving an E1 ubiquitin-activating enzyme, an E2 ubiquitin-conjugating enzyme, and an E3 ubiquitin ligase. The E3 ligase plays a crucial role in substrate specificity, dictating which proteins are ubiquitylated. Ubiquitin itself can be attached as a single molecule (monoubiquitylation) or as a chain of ubiquitin molecules (polyubiquitylation). The type of ubiquitin linkage within a polyubiquitin chain can also vary, leading to different downstream effects.

Ubiquitylation serves as a versatile molecular signal that regulates a wide array of cellular processes. Monoubiquitylation often acts as a regulatory mark, influencing protein localization, activity, or interactions. Polyubiquitylation, particularly through K48-linked chains, is a well-established signal for protein degradation via the proteasome. Other polyubiquitin chain linkages, such as K63-linked chains, are involved in non-proteolytic functions like DNA repair, signal transduction, and immune responses. The dynamic nature of ubiquitylation, with enzymes that add and remove ubiquitin (deubiquitylating enzymes or DUBs), ensures precise control over cellular events. Dysregulation of the ubiquitylation system is implicated in numerous diseases, including cancer, neurodegenerative disorders, and immune deficiencies.