Ubiquitin specific peptidase 45 (USP45)

Ubiquitin specific peptidase 45 (USP45) is a member of the ubiquitin-specific protease (USP) family and functions as a deubiquitinating enzyme that removes ubiquitin from targeted proteins, thereby reversing ubiquitination and regulating protein stability[1][4][5]. USP45 is involved in diverse cellular processes, most notably in the regulation of DNA repair through direct deubiquitination of the ERCC1 subunit of the DNA repair endonuclease XPF–ERCC1 complex, contributing to the repair of DNA interstrand cross-links and UV-induced DNA damage[3]. USP45 also regulates protein ubiquitination in cell migration—catalyzing the deubiquitination of SPDL1—and is involved in differentiation of the vertebrate retina, as well as controlling autophagy and lysosomal function via deubiquitination of actin-binding proteins such as Coronin 1B[1][2][4][5]. Pan-cancer analyses reveal USP45 is upregulated in numerous tumors, correlating with poor clinical outcomes and immune checkpoint molecule expression. Though no selective inhibitors are available, USP45 and related deubiquitinating enzymes are emerging as novel therapeutic targets for cancer and possibly neurodegenerative disorders[4][5]. If targeted therapeutically, safety concerns may include impaired DNA repair, compromised retinal or neuronal function, and disruption of proteostasis and cell migration.

Other names

Ubiquitin carboxyl-terminal hydrolase 45Deubiquitinating enzyme 45Ubiquitin thioesterase 45Ubiquitin-specific-processing protease 45LCA19MGC14793

Inhibition of USP45 would be expected to increase ubiquitination of its substrates, leading to enhanced protein degradation, altered DNA repair, and possible effects on cell migration, autophagy, and tumorigenesis