Phosphorylation and acetylation modifications of FOXO3a: Independently or synergistically?

Forkhead box class O 3a (FOXO3a) is a transcription factor that has emerged as being a tumor suppressor and longevity factor. The precise regulation of FOXO3a transactivation of target genes is achieved via post-translational modifications (PTMs) and specific protein-protein interactions. The multiple types of PTMs that FOXO3a undergoes, including phosphorylation, acetylation, methylation and ubiquitination, serve important roles in directing its subcellular localization and transcription activity, which are central to the integration of insulin/growth factor signaling and oxidative/nutrient stress signaling. The present review summarizes the modifications of FOXO3a that occur via phosphorylation and acetylation. In addition, the synergistic effect of multiple phosphorylations on FOXO3a and the crosstalk between phosphorylation and acetylation in the regulation of FOXO3a are discussed. These discussions may highlight potential strategies for the prevention of cancer and aging.