Fig. 2

The functions and regulation of FOXO3a. The non-phosphorylated form of FOXO3a located in nucleus actively mediates multiple cellular processes, including cell apoptosis, proliferation, cell cycle, survival and DNA damage by inducing transcription of its target genes depends on the upstream stimuli. The growth factor signaling induced activation of protein kinases such as PKB, ERK, SGK, IKKΒ terminate FOXO3a activity by phosphorylation (in active form). The phosphorylated FOXO3a binds with 14–3-3 protein, which consequently leads to nuclear export of FOXO3a. In the cytoplasm, FOXO3a is ubiquitinated and degraded in a proteasome-dependent manner