OTU domain-containing protein 1 (OTUD1) (OTUD1)

OTU domain-containing protein 1 (OTUD1) is a deubiquitinating enzyme (DUB) belonging to the ovarian tumor (OTU) protease family, which plays a pivotal role in maintaining cellular protein homeostasis by removing ubiquitin moieties from substrate proteins (UniProt P0C7X3). It exhibits a preference for K63-linked ubiquitin chains and is a key regulator of several major signaling cascades, including the TGF-beta, Hippo, and NF-kappaB pathways (PubMed: 29033320). In the context of oncology, OTUD1 frequently functions as a tumor suppressor; for instance, it stabilizes SMAD7 to inhibit TGF-beta-mediated epithelial-mesenchymal transition (EMT) and metastasis in breast cancer (PubMed: 33414418). It also regulates the Hippo pathway by deubiquitination and stabilization of YAP, thereby influencing cell proliferation and organ size (PubMed: 30397230). Additionally, OTUD1 is involved in innate immunity, where it stabilizes IRF3 to enhance the production of type I interferons during viral infections (PubMed: 29434354). Beyond cancer and immunity, OTUD1 has been linked to the regulation of DNA damage repair and apoptosis (PubMed: 31216453). Although no specific small-molecule drugs targeting OTUD1 are currently in clinical use, its well-defined catalytic pocket and significant role in disease progression make it an attractive target for therapeutic intervention (PubMed: 30397230). Future drug development may focus on either inhibiting its activity in inflammatory contexts or restoring its function in cancers where it is downregulated.

Other names

OTU domain-containing protein 1DUBA7OTU1HSPC157

Inhibition of the catalytic cysteine protease activity to prevent the removal of ubiquitin chains from substrate proteins.