Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.

ABSTRACT

Deubiquitinating enzymes (DUBs) are a large group of proteases that reverse ubiquitination process and maintain protein homeostasis. The DUBs have been classified into seven subfamilies according to their primary sequence and structural similarity. As a small subfamily of DUBs, the ubiquitin C-terminal hydrolases (UCHs) subfamily only contains four members including UCHL1, UCHL3, UCHL5, and BRCA1-associated protein-1 (BAP1). Despite sharing the deubiquitinase activity with a similar catalysis mechanism, the UCHs exhibit distinctive biological functions which are mainly determined by their specific subcellular localization and partner substrates. Besides, growing evidence indicates that the UCH enzymes are involved in human malignancies. In this review, the structural information and biological functions of the UCHs are briefly described. Meanwhile, the roles of these enzymes in tumorigenesis and the discovered inhibitors against them are also summarized to give an insight into the cancer therapy with the potential alternative strategy.