OTU domain-containing protein 7B (OTUD7B)

OTU domain-containing protein 7B (OTUD7B, also known as Cezanne) is a deubiquitinating enzyme belonging to the ovarian tumor (OTU) protease superfamily[1]. It possesses an OTU domain, a ubiquitin-associated (UBA) domain, and a zinc finger domain, enabling it to specifically remove polyubiquitin chains (primarily K48- and K63-linked) from substrate proteins[1][3]. OTUD7B regulates apoptosis, cell cycle, and diverse signaling cascades, notably by stabilizing p53 (reducing its proteasomal degradation), modulating non-canonical NF-κB signaling, and stabilizing TRAF2 in dendritic cells, thus balancing cell survival and inflammatory signaling[1][3]. OTUD7B displays context-dependent roles in cancer, acting as a tumor suppressor in hepatocellular carcinoma (by stabilizing p53) but promoting cancer progression in other types such as breast and pancreatic cancer via distinct substrates and pathways[1]. The enzyme is considered a promising therapeutic target for modulating the ubiquitin-proteasome system and associated disease processes, with covalent small-molecule inhibitors reported in experimental settings[2].

Other names

OTU deubiquitinase 7BZA20D1CezanneCEZANNECellular zinc finger anti-NF-kappa-B proteinZinc finger A20 domain-containing protein 1Zinc finger protein CezanneOTU domain containing 7B

Inhibitors bind covalently to the catalytic cysteine (Cys194) in the OTU domain, inhibiting deubiquitinase activity[2].