monoubiquitinering

Monoubiquitinering, also known as monoubiquitination, is a post-translational modification in which a single ubiquitin molecule is covalently attached to a substrate protein. Attachment typically occurs on a lysine residue, though in some cases ubiquitin can be added to the N-terminus. This monomeric ubiquitin state is distinct from polyubiquitination, where ubiquitin chains are formed on the substrate. A single ubiquitin moiety can alter a protein’s activity, localization, interactions, or stability without necessarily signaling for degradation.

Mechanistically, monoubiquitinering uses the core ubiquitin transfer machinery: an E1 activating enzyme, an E2 conjugating enzyme, and an E3 ligase that brings the substrate together with ubiquitin. The same enzymatic cascade can yield mono- or polyubiquitin signals, but in the case of monoubiquitination only one ubiquitin is transferred to the substrate. Reversibility is provided by deubiquitinating enzymes (DUBs), which remove ubiquitin and can restore the substrate’s prior state.

Functions of monoubiquitinering are broad. It frequently regulates endocytosis and intracellular trafficking, altering receptor or transporter localization. In chromatin biology, monoubiquitination of histones influences transcription and DNA repair: ubiquitination of histone H2B is linked to transcriptional activity, while ubiquitination of histone H2A can be associated with transcriptional repression. Monoubiquitination also modulates protein–protein interactions and signaling pathways.

Detection of monoubiquitination relies on mass spectrometry and ubiquitin-specific antibodies. Dysregulation of this modification is associated with various diseases, including cancer and neurodegenerative disorders, underscoring its importance in cellular regulation.