Ubiquitin specific peptidase 11 (USP11)

Ubiquitin specific peptidase 11 (USP11) is a cysteine protease and a member of the ubiquitin-specific protease family, functioning as a deubiquitinating enzyme that regulates protein stability by removing ubiquitin from specific protein substrates[1][2]. It plays pivotal roles in chromatin remodeling, primarily as a histone deubiquitinase for H2AK119 and H2BK120, participating directly in the DNA damage response and promoting genomic stability[1]. USP11 interacts with various key regulators, including p21, BRCA2, PALB2, Snail, and others, influencing cell cycle progression, apoptosis, EMT (epithelial-to-mesenchymal transition), and signal transduction pathways such as TGF-β, NF-κB, and Notch[1][2][4]. USP11 has context-dependent effects in cancer, acting either as an oncogene (promoting tumor growth and chemoresistance) or tumor suppressor (stabilizing proteins that inhibit cancer progression)[1][2][3]. Altered expression and activity of USP11 are linked to multiple malignancies, and it is considered a promising but complex therapeutic target, particularly for malignancies where USP11 overactivity promotes pathogenesis[2]. No specific drugs have established clinical relevance for USP11, but research into selective inhibitors is ongoing.

Other names

Ubiquitin carboxyl-terminal hydrolase 11UHX1Deubiquitinating enzyme 11Ubiquitin thioesterase 11Ubiquitin-specific-processing protease 11ubiquitin carboxyl-terminal hydrolase, X-linkedubiquitin thiolesterase 11

Drugs that target USP11 would typically act as inhibitors of its deubiquitinating activity to restore or alter protein ubiquitination and modulate downstream effects such as DNA repair, transcription regulation, or cell survival[2].