Studies in mammalian cells have shown that activation of FoxO transcription factors can induce the expression of genes involved in apoptosis (11, 16, 24-26), cell survival and differentiation (27-29), cell cycle arrest (30-33), and resistance to oxidative stress (34-37). Consistent with their capacity to regulate diverse networks of genes, the FoxOs have been linked to a number of human diseases, such as cancer (4-7, 21, 38-41) and diabetes (42-44). FoxOs also have diverse roles in developmental and reproductive biology, in which FoxO1-null mice dying on embryonic day 10 from impaired vasculogenesis (45, 46), whereas FoxO3a-null mice exhibiting premature ovarian failure (46, 47).
