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The transcriptional activity of FOXO1 is regulated in a multilayered manner. EWS-FLI1 not only represses the transcription of FOXO1 but also affects P-AKT levels and regulates CDK2 activity, thus regulating FOXO1 transcriptional activity on a post-translational level. Blocking the PI3K-AKT signaling pathway with the canonical PI3K inhibitor LY294002 or by blocking active CDK2 with roscovitine can overcome the repressive effect of EWS-FLI1 as shown for ectopically expressed FOXO1wt.
