Figure 2. Regulation of FoxM1 activity and its downstream target molecules.

FoxM1 is positively regulated by sonic hedgehog, Ras/MEK/ERK, and cyclin E/Cdk2 growth signaling pathways, among others, and inhibited by the tumor suppressor p19^ARF. FoxM1 directly or indirectly modulates a number of cell cycle (replication/mitosis) regulators to promote cell proliferation and affects the signal pathways essential for organogenesis, including TGF-β signaling and VEGF signaling, thereby contributing to tissue regeneration, tumorigenesis, and organogenesis during embryonic development. Cdc25A, cell division cycle 25A; Cdc25B, cell division cycle 25B; CENP, centromere protein; Plk-1, polo-like kinase-1; p19^ARF, 19-kDa alternative reading frame protein.