FoxO signaling pathway (FOXO signaling pathway)

The FoxO signaling pathway is a collection of regulatory interactions involving the FOXO subfamily of forkhead box transcription factors (FOXO1, FOXO3, FOXO4, FOXO6 in mammals). FOXOs are master regulators that control genes involved in cell cycle arrest, apoptosis, metabolism, oxidative stress resistance, and immune function. The pathway is tightly regulated by insulin and growth factor signaling, mainly through PI3K/AKT-mediated phosphorylation, which causes FOXO proteins to exit the nucleus and become transcriptionally inactive. Under conditions like oxidative stress, nutrient deprivation, or loss of growth signals, FOXO proteins are dephosphorylated and translocate into the nucleus to activate gene expression programs for cellular stress resistance and metabolic adaptation. Dysregulation of FOXO signaling has important implications in cancer, aging, metabolic disorders, and cardiovascular and neurodegenerative diseases.

Other names

Forkhead box O signalingFOXO pathwayForkhead box protein O signaling

Drugs typically modulate upstream regulators (e.g., activate or inhibit PI3K/AKT) to control FOXO nuclear localization and activity, leading to activation or inhibition of FOXO-dependent transcriptional programs.