Ubiquitineren

Ubiquitineren, or ubiquitination, is a post-translational modification in which ubiquitin, a small regulatory protein, is covalently attached to substrate proteins. The process relies on a sequential enzyme cascade: an E1 activating enzyme forms a thioester bond with ubiquitin in an ATP-dependent reaction, an E2 conjugating enzyme transfers ubiquitin to an E3 ligase, and the E3 ligase facilitates the transfer of ubiquitin to a lysine residue on the substrate or on another ubiquitin. This can result in monoubiquitination or polyubiquitination, where ubiquitin molecules form chains through lysine residues on ubiquitin itself.

Ubiquitin chains vary by linkage type, and different linkages elicit different cellular outcomes. Monoubiquitination or short chains can regulate protein localization, activity, or interactions, while polyubiquitin chains commonly signal for proteasomal degradation, particularly those linked through lysine 48. Other linkages, such as lysine 63, lysine 11, or branched chains, participate in signaling, DNA repair, endocytosis, and trafficking without necessarily marking the protein for destruction.

The ubiquitination state of a protein is reversible, controlled by deubiquitinating enzymes (DUBs) that remove ubiquitin and by chain-editing activities that shape signaling outcomes. Ubiquitination thus serves as a versatile regulatory code that influences proteostasis, cell cycle progression, immune responses, and many other cellular processes.

Dysregulation of ubiquitination is implicated in numerous diseases, including cancer and neurodegenerative disorders. Because of its central role in protein homeostasis and signaling, ubiquitination components are active areas of biomedical research and therapeutic development.