Ubiquitin Specific Peptidase 47 (USP47)

USP47 as a novel interactor of the E3 ubiquitin ligase, Skp1/Cul1/F-box protein β-transducin repeat-containing protein. Both β-Trcp1 and β-Trcp2 bind specifically to USP47, and point mutations in the β-Trcp WD-repeat region completely abolished USP47 binding, indicating an E3-substrate-type interaction. USP47 protein levels were neither affected by silencing of β-Trcp nor modulated in a variety of processes, such as cell-cycle progression, DNA damage checkpoint responses or tumor necrosis factor (TNF) pathway activation. Notably, genetic or siRNA-mediated depletion of USP47 induced accumulation of Cdc25A, decreased cell survival and augmented the cytotoxic effects of anticancer drugs. USP47, a novel β-Trcp interactor, regulates cell growth and survival, potentially providing a novel target for anticancer therapies.