Regulation of Foxo-Dependent Transcription by Post-Translational Modifications

The Forkhead Box O (Foxo) proteins represent an evolutionarily conserved family of transcription factors that play an important role in regulating processes including metabolism, longevity, and cell death/survival. How is it that a single transcription factor can initiate such divergent cellular responses? We will review the evidence that specific patterns of post-translational modifications play a key role in directing Foxo into various transcriptional readouts. This regulation appears to take on a two tiered regulatory model; with a group of well defined post-translational modifications regulating nuclear localization and transcriptional activity while a second set of modifications regulate the transcriptional specificity of Foxo Keywords: Foxo, post-translational modifications, phosphorylation, acetylation, ubiquitination, Drosophila, Caenorhabditis, Nuclear localization sequence, DYRK1A, MST1, AMPK, SIRT1, MDM2, USP7