Induction of Wip1 after UV radiation also appears to be dose-dependent (60, 61). Low doses of Ultraviolet C (UVC, 240–290 nm) radiation, such as 5 J/m2, induce Wip1 expression as expected. In contrast, Wip1 is not induced and its expression actually decreases after a high dose of UVC radiation, such as 50 J/m2 (61). Using actinomycin D to inhibit transcription and MG132 to inhibit proteasome-dependent protein degradation, Xia et al. showed that Wip1 is down-regulated after high doses of UVC at the transcription and protein level. They determined that this is independent of p53, but did not elucidate the mechanism by which PPM1D transcription is inhibited and the Wip1 protein is destabilized. However, as described above, the lack of Wip1 induction may result from the presence of unrepaired DNA lesions at this high dose of UVC radiation and the consequent block of PPM1D transcription (59, 60). Additionally, the sustained phosphorylation of p53 on S15 and increased level of apoptosis that result from exposure to high doses of UVC radiation are consistent with the lack of Wip1 induction (61). The authors
