Ubiquitin specific peptidase 51 (USP51)

Ubiquitin specific peptidase 51 (USP51) is a member of the ubiquitin-specific protease (USP) family of deubiquitinating enzymes. USP51 regulates the stability and function of several substrates by removing ubiquitin moieties, including the histone H2A (at Lys-13 and Lys-15), the DNA repair factor DGCR8, and the transcriptional repressor ZEB1. Through these activities, USP51 is involved in the regulation of DNA double-strand break repair, chromatin remodeling, cell cycle progression, and gene transcription. Overexpression of USP51 has been observed in human cancers such as breast cancer, where it promotes invasion, metastasis, epithelial-mesenchymal transition, and therapy resistance by stabilizing ZEB1. Aberrant USP51 activity is associated with poor prognosis in cancer, and the enzyme is considered a potential therapeutic target due to the druggable nature of deubiquitinating enzymes; however, specific pharmacological inhibitors have not yet been reported for USP51.

Other names

Ubiquitin carboxyl-terminal hydrolase 51Deubiquitinating enzyme 51Ubiquitin thioesterase 51Ubiquitin-specific-processing protease 51USP51

For theoretical USP51 inhibitors: inhibition of deubiquitinase activity, leading to increased ubiquitination and degradation of target proteins (e.g., ZEB1, histone H2A), potentially reducing metastasis and therapy resistance