Fig. 1. Domain structure of the FoxO1 protein (A) and the major post-translational modifications or protein interactions within and near the forkhead (FKH) domain and the nuclear localization signal (NLS) (B). NES, nuclear export signal; TA, the transactivation domain. The secondary structures predicted from the FKH domain of HNF-3 – four -helices (H1, H2, H3 and H4) and two winged-loops (W1 and W2) – are included. Residues representing the identified or potential post-translational modifications, and the site for interaction with Skp2, that inhibit FoxO1 are indicated in red; those that promote FoxO1 activity are in green. Preferred Akt- and SGK-phosphorylation sites are underlined.