Ubiquitin specific peptidase 37 (USP37)

Ubiquitin specific peptidase 37 (USP37) is a cysteine-type deubiquitinase enzyme located in the nucleus, playing a crucial role in removing ubiquitin chains from specific substrate proteins. USP37 regulates the G1/S transition of the cell cycle by antagonizing the anaphase-promoting complex (APC/C) and stabilizing key cell cycle proteins such as cyclin A. It further controls DNA replication by stabilizing licensing factors and checkpoint kinases (e.g., CHK1), thus promoting efficient and accurate DNA replication and enhancing the cellular response to replication stress. USP37 is involved in maintaining genome stability, supporting DNA damage response, and modulating cell proliferation and migration via deubiquitination of target proteins, such as 14-3-3γ and EMT transcription factors. Elevated USP37 expression promotes cellular transformation and proliferation, making it a potential therapeutic target, especially in cancer. Disease relevance includes cancer progression and neurodegenerative disorders. Current research is focused on USP37's mechanistic roles in tumorigenesis, though direct pharmacological targeting remains under early development.

Other names

USP37Ubiquitin carboxyl-terminal hydrolase 37KIAA1594Deubiquitinating enzyme 37Ubiquitin thioesterase 37Ubiquitin-specific-processing protease 37tmp_locus_50

For prospective inhibitors: block deubiquitinase activity, thereby destabilizing target proteins (such as cyclin A and checkpoint kinases like CHK1), leading to cell cycle arrest, enhanced DNA damage, and apoptosis in cancer cells.