Description
FOXO4 is a member of the forkhead family of transcription factors in O subclass, which is characterized by a winged helix domain used for DNA binding.
[7][8] There are 4 members of the FOXO family, including
FOXO1,
FOXO3, and
FOXO6. Their activity is modified by many post translational activities, such as phosphorylation, ubiquitination, and acetylation.
[9] Depending on this modified state, FOXO4 binding affinity for DNA is altered, allowing for FOXO4 to regulate many cellular pathways including
oxidative stress signaling, longevity, insulin signaling, cell cycle progression, and apoptosis.
[10][11][12][13][14] Two of the main upstream regulators of FOXO4 activity are
phosphoinositide 3- kinase (PI3K) and serine/threonine kinase
AKT/PKB.
[15][16] Both PI3K and AKT modify FOXO4 and prevent it from translocating to the nucleus, effectively preventing the transcription of the downstream FOXO targets.
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