Fig. 1.

FOXO regulation through posttranslational modifications. (A) General domain structure of the FOXO family of transcription factors. The conserved DNA binding domain is termed the Forkhead box. NES, nuclear export signal; NLS, nuclear localization signal. (B) FOXOs are posttranslationally modified by a number of different enzymes that affect their transcriptional activity. FOXOs are also regulated at the posttranscriptional level by several different miRNAs. Proteins and miRNAs that have been identified as direct regulators of FOXOs in mammalian cells are listed. Note that proteins in red perform the opposite function than the categorized covalent modification (i.e., PTEN and PP2A are phosphatases and HDAC3 and SIRT1 are deacetylases).