Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3)

Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) is a member of the deubiquitinating enzyme (DUB) family, specifically within the UCH (ubiquitin carboxyl-terminal hydrolase) subclass. UCHL3 is a cysteine protease that hydrolyzes ubiquitin or NEDD8 adducts from substrate proteins, thereby maintaining cellular ubiquitin levels and regulating protein turnover and cellular signaling. The enzyme is involved in protein homeostasis, cell cycle regulation, DNA repair, and signal transduction, with its expression found in diverse tissues, including the brain, muscle, and testis. Structurally, it shares the papain-like cysteine protease fold and possesses a conserved catalytic triad (Cys-His-Asp), and substrate recognition is modulated by conformational changes. Pathologically, UCHL3 is linked to cancer stemness, several cancers, and neurodegenerative diseases, making it a promising therapeutic target, though safety and specificity concerns remain important for drug development[1][2][3][4][5].

Other names

Ubiquitin thioesterase L3Ubiquitin thiolesteraseUbiquitin carboxyl-terminal esterase L3Ubiquitin C-terminal hydrolase L3UCH-L3Testicular tissue protein Li 221

Inhibitors block the deubiquitylation activity, leading to target protein (e.g., AhR) degradation. Modulation of stem cell-related genes via AhR stability (affecting ABCG2, KLF4, c-Myc). Indirect modulation of signaling pathways (e.g., IGFIR/AKT/FOXO1).