Introduction to FOXO Biology

Forkhead box O (FOXO) proteins are a family of transcription factors with four members in mammals, namely FOXO1, FOXO3a, FOXO4, and FOXO6. FOXO factors, originally identified as downstream regulators of the insulin pathway, are known to bind to the promoters of a broad variety of target genes and control several processes of key importance for cellular homeostasis including cellular energy production, oxidative stress resistance, and cell viability and proliferation. Accordingly, deregulation of FOXO proteins has been shown to play an essential role in metabolic disorders, human longevity, and the suppression of tumors. As the activity of these transcription factors is controlled by posttranslational modifications, inactivation of FOXOs occurs mostly due to the overactivation of their upstream modifying enzymes providing a wealth of possibilities for restoring FOXO activity pharmaceutically.