deubiquitinates

Deubiquitination is the biochemical process by which ubiquitin, a small regulatory protein, is removed from substrate proteins. This reaction is carried out by deubiquitinases, enzymes that oppose ubiquitination and serve to regulate protein stability, signaling, and trafficking within the cell.

DUBs are diverse in mechanism and location. They include cysteine proteases such as ubiquitin-specific proteases (USPs), ubiquitin C-terminal hydrolases (UCHs), the ovarian tumor domain-containing proteases (OTUs), and related families. Metalloenzymes in the JAMM/MPN+ family also remove ubiquitin. Some DUBs are associated with the proteasome or with specific cellular compartments, and others function in the nucleus, cytoplasm, or organelles.

Deubiquitination can stabilize proteins by removing degradation-promoting ubiquitin signals, but it can also edit ubiquitin chains to alter signaling outcomes without fully rescuing degradation. The effect depends on the ubiquitin linkage type (for example, K48-linked chains commonly tag proteins for degradation, whereas K63-linked chains regulate signaling and trafficking) and on the substrate context.

DUB activity is tightly controlled and can be altered by cellular signals, post-translational modifications, and interacting partners. Misregulation of deubiquitination has been linked to cancer, neurodegenerative diseases, and infections, making DUBs targets for therapeutic interventions and drug discovery.

In research, deubiquitinases are studied using biochemical assays and ubiquitin-based probes, genetic approaches, and structural biology to understand substrate specificity and regulation.