OTU domain-containing protein 3 (OTUD3)

OTU domain-containing protein 3 (OTUD3) is a cysteine protease and member of the OTU family of deubiquitinases, which selectively cleaves ubiquitin chains from substrate proteins, most notably Lys6- and Lys63-linked chains. OTUD3 is involved in multiple cellular processes including stabilization of tumor suppressors (e.g., PTEN, p53), regulation of metabolic proteins (e.g., IRP2, PPARδ), control of innate immunity (viral response via MAVS, RIG-I, cGAS), and negative regulation of ribosomal protein ubiquitination. Expression and function of OTUD3 are tightly regulated by post-translational modifications and microRNAs. It is abnormally expressed in many cancers and diseases, acting variably as a tumor suppressor or oncogene. OTUD3 has emerged as a promising therapeutic target with experimental small-molecule inhibitors being developed for cancer and other diseases.

Other names

OTUD3OTU deubiquitinase 3OTU domain containing 3KIAA0459DUBA4

Inhibition of deubiquitinase activity (by small molecule inhibitors like OTUDin3) reduces stabilization of OTUD3 substrates, promoting their degradation and impacting tumorigenesis. Deubiquitination of specific lysine-linked ubiquitin chains (primarily Lys6 and Lys63, but also Lys11, Lys27, and Lys48) on substrate proteins, affecting their stability and downstream signaling.