Ubiquitin-specific protease 25 (USP25)

Ubiquitin-specific protease 25 (USP25) is a cysteine protease belonging to the family of deubiquitinating enzymes (DUBs), which catalyze the removal of ubiquitin chains from target proteins to regulate their stability, localization, and activity[2][4]. USP25 has a modular structure with a catalytic domain and multiple ubiquitin-binding regions, including ubiquitin-associated domains and SUMO-interacting motifs. It exists in several tissue-specific isoforms, including USP25a, USP25b, and USP25m. USP25’s enzymatic activity is auto-regulated by a unique tetrameric assembly that can inhibit substrate binding[3]. USP25 regulates diverse biological processes, including protein degradation by the ubiquitin-proteasome and autophagy-lysosomal pathways, modulation of cell signaling (such as Wnt/β-catenin and TAK1/MAPK), control of immune responses, and cell migration and invasion. Dysregulation of USP25 contributes to pathological conditions including cancer, neurodegenerative diseases, inflammation, cardiovascular diseases, viral infections, and miscarriage. USP25 is considered a promising therapeutic target, and modulation of its activity is being investigated for drug development[1][2][3][4][5].

Other names

Ubiquitin carboxyl-terminal hydrolase 25Deubiquitinating enzyme 25USP on chromosome 21Ubiquitin thioesterase 25Ubiquitin-specific-processing protease 25EIG19USP25a, USP25b, USP25m (isoforms)

Inhibition or activation of enzymatic deubiquitination, influencing the stabilization or degradation of specific cellular proteins (e.g., tankyrases, P62) Modulation of cell signaling pathways by altering ubiquitin chain status (Lys48- vs Lys63-linked)