E2F1 and neoplasm: Given that ligands of nuclear receptors such as PB and TCPOBOP have been shown to cause liver polyploidization (59,67,68), we propose that both E2F1 and E2F8 are responsible for the E2F activity modulation at the tumor stage and that they regulate distinct cell cycle checkpoints, in particular, regulation of entry in S-phase for E2F1 and inhibition of cytokinesis for E2F8 together with Myc (Figure 6b).