E2F1 is a member of the E2F family of transcription factors that regulates genes important for cell growth, cell differentiation and apoptosis (29–31). As shown in Figure 1, an E2F family binding motif is present in the PPM1D promoter at −652 base pairs from the translation start site (32). Hershko et al. showed that PPM1D is a target of E2F1 by RT-PCR and ChIP analysis (Figure 2). Furthermore, E2F1 modulates PPM1D transcription independently of p53, since cells in which E2F1 is conditionally activated and that have depleted p53 by siRNA show a similar increase in Wip1 expression compared to cells that fully express p53. The fact that E2F1 upregulated Wip1 in a p53-deficient lung carcinoma cell line, H1299, also indicated that E2F1 induction of Wip1 is independent of p53 (32). It may be worth noting, however, that these experiments were done in cell systems in which E2F1 is conditionally activated upon the addition of a 4-hydroxytamoxifen rather than through its intrinsic regulation.
