Forkhead box O transcription factor (FOXO)

Forkhead box O transcription factors (FOXO), including FOXO1, FOXO3, FOXO4, and FOXO6, are members of the forkhead box family of transcription factors defined by a conserved winged-helix DNA-binding domain[1][3][5]. FOXO proteins regulate the expression of genes involved in metabolism, cell cycle control, apoptosis, autophagy, redox balance, and cell differentiation, and are essential for adaptation to metabolic and oxidative stress and for maintenance of cellular and organismal homeostasis[1][2][4][7]. FOXO activity is regulated by posttranslational modifications including phosphorylation, acetylation, and ubiquitination in response to growth factors, oxidative stress, and nutrient status[1][9]. Dysregulation of FOXO function is implicated in diseases such as cancer, diabetes, neurodegenerative disorders, and cardiovascular disease, making FOXO transcription factors targets for novel therapeutic strategies[1][4][7][8].

Other names

FOXO transcription factorFOXO proteinForkhead in rhabdomyosarcoma (FKHR, specifically for FOXO1)Forkhead proteins of class O

Drugs may modulate FOXO function indirectly via upstream inhibition of the PI3K/AKT/mTOR pathway, leading to FOXO activation and nuclear localization[1][4]; modulation of phosphorylation, acetylation, and ubiquitination affects FOXO activity[1][9].