Abstract
E2F1, a member of the E2F family of transcription factors, in addition to its established proliferative effect1, has also been implicated in the induction of apoptosis through p53-dependent and p53-independent pathways2. Several genes involved in the activation or execution of the apoptotic programme have recently been shown to be upregulated at the transcriptional level by E2F1 overexpression, including the genes encoding INK4a/ARF, Apaf-1, caspase 7 and p73 (refs 3–5). E2F1 is stabilized in response to DNA damage6,7 but it has not been established how this translates into the activation of specific subsets of E2F target genes. Here, we applied a chromatin immunoprecipitation approach to show that, in response to DNA damage, E2F1 is directed from cell cycle progression to apoptotic E2F target genes. We identify p73 as an important E2F1 apoptotic target gene in DNA damage response and we show that acetylation is required for E2F1 recruitment on the P1p73 promoter and for its transcriptional activation.
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Acknowledgements
We thank P. Lavia, G. Blandino, P.L. Puri, M. Fanciulli and E. De Smaele for reading the manuscript critically and for helpful suggestions. This work was supported by grants from AIRC, MURST-Cofin, MURST-FIRB, Ministry of Health and Telethon to M.L., from AIRC, the Ministry of University and Research, National Research Council – 'Oncology' Project, the Ministry of Health MURST-CNR 'Biomolecole per la Salute Umana' Program and Center of Excellence BEMM to A.G.; from AIRC and Cenci-Bolognetti Foundation, Pasteur Institute, to I.S. and from the Ministry of Health to E.A. N.P. and L.B. are supported by fellowships from the Fondazione A. Cesalpino. R.G. is supported by a fellowship from FIRC.
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Pediconi, N., Ianari, A., Costanzo, A. et al. Differential regulation of E2F1 apoptotic target genes in response to DNA damage. Nat Cell Biol 5, 552–558 (2003). https://doi.org/10.1038/ncb998
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DOI: https://doi.org/10.1038/ncb998
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