As discussed in section 3, both c-jun and p53 have been shown to contribute to Wip1 induction after UV radiation exposure (4, 28). Song et al. showed by ChIP analysis that p53 binding to the PPM1D promoter peaks very soon after UV radiation exposure, after approximately 1 hour, whereas c-jun binding peaks at about 5 hours after UV radiation exposure in A549 cells. Additionally, JNK kinase activity upstream from c-jun is required for c-jun-mediated Wip1 induction, as indicated by reduced Wip1 expression in the presence of a JNK inhibitor. Therefore, in addition to the BRCA1-IRIS-dependent mechanism discussed in section 3.1.2, two additional signaling pathways lead to UV radiation-induced Wip1 expression – the JNK/c-jun pathway and the p38 MAPK/p53 pathway (28).
