UV-induced degradation of securin is mediated by SKP1-CUL1-TrCP E3 ubiquitin ligase

Securin is a chaperone protein with bifunctional properties. It binds to separase to inhibit premature sister chromatid separation until the onset of anaphase, and it also takes part in cell-cycle arrest after UV irradiation. At metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome (APC/C), allowing activation of separase. However, although securin is reported to undergo proteasome-dependent degradation after UV irradiation, the ubiquitin ligase responsible for securin ubiquitylation has not been well characterized. In this study, we show that UV radiation induced a marked reduction of securin in both the nucleus and cytoplasm. Moreover, we show that GSK-3 inhibitors prevent securin degradation, and that CUL1 and TrCP are involved in this depletion. We also confirmed that SKP1-CUL1-TrCP (SCF^TrCP) ubiquitylates securin in vivo, and identified a conserved and unconventional TrCP recognition motif (DDAYPE) in the securin primary amino acid sequence of humans, nonhuman primates and rodents. Furthermore, downregulation of TrCP caused an accumulation of securin in non-irradiated cells. We conclude that SCF^TrCP is the E3 ubiquitin ligase responsible for securin degradation after UV irradiation, and that it is involved in securin turnover in nonstressed cells.