The cunning little vixen: Foxo and the cycle of life and death

A screen for increased longevity in Caenorhabditis elegans has identified a transcription factor that programs cells for resistance to oxidative stress, DNA repair and cell cycle control. The mammalian orthologs of this factor are referred to as 'Foxo' for 'Forkhead box', with the second 'o' in the name denoting a subfamily of four members related by sequence. This family of factors is regulated by growth factors, oxidative stress or nutrient deprivation. Thus, it might readily control the inflammatory conflagration associated with infection-driven lymphocyte proliferation. Surprisingly, the first insights into Foxo-mediated immune regulation have instead revealed direct control of highly specialized genes of the adaptive immune system.