FOXO Transcription Factors: A Brief Overview

Forkhead box O (FOXO) transcription factors constitute a mammalian family of proteins, comprising FOXO1, FOXO3, FOXO4, and FOXO6. Originally recognized as downstream regulators within the insulin pathway, FOXO factors exhibit the ability to bind to diverse target gene promoters, thereby governing crucial facets of cellular homeostasis. These encompass cellular energy generation, resilience against oxidative stress, and the modulation of cell viability and proliferation. The dysregulation of FOXO proteins has been established as pivotal in metabolic disorders, human longevity, and the inhibition of tumorigenesis. Notably subject to posttranslational modifications for regulation, FOXO inactivation predominantly arises from excessive activation of their upstream modifying enzymes, presenting a plethora of potential avenues for pharmaceutical reinstatement of FOXO activity.