Letter abstract
Nature Cell Biology 5, 552 - 558 (2003)
Published online: 19 May 2003 | doi:10.1038/ncb998
Differential regulation of E2F1 apoptotic target genes in response to DNA damage
Natalia Pediconi1,8, Alessandra Ianari2,8, Antonio Costanzo1,3,8, Laura Belloni1, Rita Gallo4, Letizia Cimino1, Antonio Porcellini5, Isabella Screpanti2, Clara Balsano1,6, Edoardo Alesse4, Alberto Gulino2,5 & Massimo Levrero1,7
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.
- Laboratory of Gene Expression, Fondazione Andrea Cesalpino, University of Rome 'La Sapienza', Viale del Policlinico 155, 00161 Rome, Italy.
- Dipartimento Medicina Sperimentale e Patologia, University of Rome 'La Sapienza', Viale Regina Elena 324, 00161 Rome, Italy.
- Department of Dermatology, University of Rome 'Tor Vergata', Viale Oxford 81, 00133 Rome, Italy.
- Dipartimento Medicina Sperimentale, University of L'Aquila, Via Vetoio 10, 67100 L'Aquila, Italy.
- Istituto Neuromed, Pozzilli 86077, Italy.
- Dipartimento Medicina Interna, University of L'Aquila, Via S. Sisto 22 E, 67100 L'Aquila, Italy.
- Dipartimento Scienze Mediche Internistiche, University of Cagliari, Via S. Giorgio 12, 09124 Cagliari, Italy
- These authors contributed equally to this work.
Correspondence to: Alberto Gulino2,5 e-mail: alberto.gulino@uniroma1.it
Correspondence to: Massimo Levrero1,7 e-mail: levmax@tin.it
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