FOXO3
FOXO3 is a forkhead transcription factor that activates genes for DNA repair, autophagy, antioxidant defense, and stress resistance when insulin/IGF-1 signaling is low.
Function
Insulin and IGF-1 signaling activates AKT, which phosphorylates FOXO3 and keeps it outside the nucleus. When those signals fall - fasting, calorie restriction, stress - FOXO3 enters the nucleus and activates a transcriptional program of maintenance: antioxidant enzymes (SOD2, catalase), DNA-repair genes, autophagy genes, cell-cycle arrest through p21 and p27-family inhibitors, and stress-resistance proteins. FOXO3 mediates the longevity phenotype that reduced insulin/IGF signaling produces across species: in C. elegans, the FOXO ortholog DAF-16 is the effector of daf-2 longevity.
In aging and cancer
FOXO3 is one of the
Log in and become a supporter to read the full article.
Become a supporter to read the full article.