monoubiquitinylation

Monoubiquitinylation is a post-translational modification where a single ubiquitin molecule is attached to a substrate protein. Ubiquitin is a small, highly conserved protein that acts as a tag to signal changes in the modified protein's fate or function. This modification is distinct from polyubiquitinylation, where multiple ubiquitin molecules are linked together to form a chain.

The process of monoubiquitinylation is catalyzed by a cascade of enzymes known as E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin ligase). The E1 enzyme activates ubiquitin, which is then transferred to an E2 enzyme. Finally, an E3 ligase facilitates the transfer of the activated ubiquitin to a specific lysine residue on the target protein. The specificity of the modification is largely determined by the E3 ligase.

Monoubiquitinylation can occur on various proteins, including histones, transcription factors, and signaling molecules. Unlike polyubiquitinylation, which often targets proteins for proteasomal degradation, monoubiquitinylation typically regulates protein localization, activity, or interactions. For instance, monoubiquitinylation of histone H2A is involved in transcriptional regulation and DNA repair. Monoubiquitinylation of endocytic proteins is crucial for their trafficking within the cell. The reversibility of monoubiquitinylation, mediated by deubiquitinating enzymes (DUBs), allows for dynamic control of protein function.