Ubiquitination is a cellular process by which a small regulatory protein called ubiquitin is attached to a substrate protein. This protein modification can target the substrate for degradation through the proteasome, alter its cellular location, affect its activity or promote/prevent protein interactions. The subsequent disassembly of polyubiquitin chains and release of ubiquitin from the degraded protein, a process known as deubiquitination, is carried out by ubiquitin-specific proteases such as USP2.
USP2 belongs to the peptidase C19 superfamily and targets polyubiquitinated proteins such as MDM2, MDM4 and cyclin D1. As MDM2 and MDM4 are negative regulators of the p53 tumor suppressor, USP2 indirectly promotes p53/TP53 degradation and limits p53 activity. Through cyclin D1, USP2 plays a role in the G1/S cell-cycle progression in normal and cancer cells. The protein is also involved in the biological processes of circadian behavior, locomotor rhythm and regulation of skeletal muscle tissue development.