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Biochim Biophys Acta. 2007 Apr;1769(4):244-52. Epub 2007 Apr 6.

E2F-1 regulates expression of FOXO1 and FOXO3a.

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Institute of Molecular Biology and Tumor Research (IMT), Emil-Mannkopff-Strasse 2, 35033 Marburg, Germany.


E2F and FOXO transcription factors both play a role in neuronal apoptosis. In addition, both E2F-induced apoptosis and FOXO function are inhibited by the kinase Akt. We therefore tested whether FOXO is downstream of E2F-1 during neuronal apoptosis. We found that expression of endogenous FOXO1 and FOXO3a is induced by E2F-1. The presence of putative E2F binding sites in the promoters of both genes suggested that FOXO genes are direct targets of E2F-1. Indeed, a 4-hydroxytamoxifen activated E2F-1-ER fusion protein induced FOXO expression in the presence of cycloheximide. Moreover, E2F-1 activated the FOXO1 promoter in transient reporter assays, and E2F-1-ER as well as endogenous E2F bound to the FOXO1 promoter in vivo. Yet, E2F-1-mediated apoptosis of differentiated PC12 cells after withdrawal of NGF was not accompanied by changes in FOXO expression, indicating that no transcriptional induction of FOXO occurs during E2F-1-dependent neuronal apoptosis. In summary, our data identify E2F-1 as a first transcription factor regulating FOXO expression, providing a link between E2F and FOXO proteins in the control of cell fate.

[Indexed for MEDLINE]

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