Ubiquitin carboxyl-terminal hydrolase 20 (USP20)

Ubiquitin carboxyl-terminal hydrolase 20 (USP20) is a member of the ubiquitin-specific protease family of deubiquitinating enzymes, characterized as a cysteine protease[1][3]. It catalyzes the removal of ubiquitin moieties from target proteins, regulating their stability by preventing proteasomal degradation. USP20 contains an N-terminal zinc finger ubiquitin-binding domain (ZnF-UBP), a USP catalytic domain, and two C-terminal DUSP domains[2][3]. It acts on substrates such as hypoxia-inducible factor 1α (HIF1α), thyronine deiodinase type 2 (D2), β2-adrenergic receptor (β2AR), ULK1, MCL1, and others, controlling key biological processes including cell cycle progression, apoptosis, cell migration, autophagy, and responses to hypoxia[1][2][3][4][5][7]. USP20 dysregulation and overexpression have been implicated in multiple cancer types and contribute to tumorigenesis, metastasis, and chemotherapy resistance[3][6][7]. Although no approved therapies target USP20 directly, it is considered a promising therapeutic target for cancer and other disorders involving aberrant protein turnover[2][3][7].

Other names

KIAA1003LSFR3AVDU2hVDU2Deubiquitinating enzyme 20Ubiquitin thioesterase 20Ubiquitin-specific-processing protease 20VHL-interacting deubiquitinating enzyme 2pVHL-interacting deubiquitinating enzyme 2

USP20 inhibitors aim to block USP20’s deubiquitinating activity, leading to increased degradation of substrate proteins such as HIF1α, thereby interfering with cellular adaptation to hypoxia and potentially reducing tumor growth.