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9623899
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Localization of FOXO transcription factors FOXO1, FOXO3 and ...
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Summation
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Localization of FOXO transcription factors FOXO1, FOXO3 and FOXO4 is regulated by AKT-mediated phosphorylation. In the absence of PI3K/AKT signaling, FOXO1, FOXO3 and FOXO4 localize to the nucleus. AKT-mediated phosphorylation induces a conformational change that exposes a nuclear export signal (NES) and promotes translocation of FOXO1, FOXO3 and FOXO4 to the cytosol (Rena et al. 1999, Brunet et al. 1999, Kops et al. 1999). AKT-phosphorylated FOXO1, FOXO3 and FOXO4 bind to 14-3-3 proteins, which contributes to their retention in the cytosol (Rena et al. 2001, Brunet et al. 1999, Arimoto Ishida et al. 2004, Obsilova et al. 2005, Boura et al. 2007, Silhan et al. 2009). FOXO6 lacks the NES sequence and is exclusively nuclear, but phosphorylation in response to PI3K/AKT signaling affects the transcriptional activity of FOXO6 (Jacobs et al. 2003, van der Heide et al. 2005).