Deubiquitinase Usp18 prevents cellular apoptosis from oxidative stress in liver cells

Deubiquitinases (DUBs) deconjugate ubiquitin (UBQ) from ubiquitylated substrates to regulate their activity and stability. They play different cellular functions such as cell cycle regulation, DNA repair, and early embryogenesis. Additionally, studies have demonstrated that some DUBs are the signaling targets of cellular stress such as oxidative stress. Reactive oxygen species are generated during normal mitochondrial oxidative metabolism and proper cellular mechanism could protect the cell from the oxidative stress. However, there are limited studies that specifically focus on the role of DUBs in oxidative stress, and thus the underlying protective mechanism by DUBs is not yet known. The report here, for the first time, applied the mouse-specific DUB RT2 Profiler PCR array to identify DUBs that are responsive to oxidative stress. Out of the tested 83 DUBs, 15 of them were found to be differentially expressed. Among them, Usp18 was found to be induced with a dose- and time-dependent manner of oxidative stress. In functional studies, depletion of Usp18 could stimulate the p53 and caspase 3 protein levels. In addition, knockdown of Usp18 could lead to the reduced cell viability and increased in apoptotic cell death under oxidative stress. Collectively, Usp18 protects the cells from oxidative stress-induced apoptosis which may be through the regulation of p53 and caspase 3.