As discussed above, p38 MAPK/p53 signaling is important for Wip1 induction after UV radiation exposure (4). However, a recent report by Song et al. showed that JNK/c-jun signaling contributes to Wip1 induction in A549 cells (28). A sequence matching a c-jun binding motif is located 283 bp upstream from the translation start site in the PPM1D promoter region, overlapping the CRE (Figure 1). Overexpression of c-jun enhanced UV radiation-induced Wip1 promoter activity, and Electophoretic Mobility Shift Assays (EMSAs) indicated that c-jun directly bound to the consensus sequence in the PPM1D promoter region (28). ChIP assays demonstrated that p53 was bound to the Wip1 promoter a short time after UV radiation exposure, and JNK-activated c-jun was bound later (28). Therefore, the JNK/c-jun pathway may contribute to the UV-induced induction of Wip1 (Figure 2).
