Ubiquitin carboxyl-terminal hydrolases: involvement in cancer progression and clinical implications

Protein ubiquitination and deubiquitination participate in a number of biological processes, including cell growth, differentiation, transcriptional regulation, and oncogenesis. Ubiquitin C-terminal hydrolases (UCHs), a subfamily of deubiquitinating enzymes (DUBs), includes four members: UCH-L1/PGP9.5 (protein gene product 9.5), UCH-L3, UCHL5/UCH37, and BRCA1-associated protein-1 (BAP1). Recently, more attention has been paid to the relationship between the UCH family and malignancies, which play different roles in the progression of different tumors. It remains controversial whether UCHL1 is a tumor promoter or suppressor. UCHL3 and UCH37 are considered to be tumor promoters, while BAP1 is considered to be a tumor suppressor. Studies have showed that UCH enzymes influence several signaling pathways that play crucial roles in oncogenesis, tumor invasion, and migration. In addition, UCH families are associated with tumor cell sensitivity to therapeutic modalities. Here, we reviewed the roles of UCH enzymes in the development of tumors, highlighting the potential consideration of UCH enzymes as new interesting targets for the development of anticancer drugs.