Differential regulation of E2F1 apoptotic target genes in response to DNA damage

Natalia Pediconi; Alessandra Ianari; Antonio Costanzo; Laura Belloni; Rita Gallo; Letizia Cimino; Antonio Porcellini; Isabella Screpanti; Clara Balsano; Edoardo Alesse; Alberto Gulino; Massimo Levrero

doi:10.1038/ncb998

Differential regulation of E2F1 apoptotic target genes in response to DNA damage

Nat Cell Biol. 2003 Jun;5(6):552-8. doi: 10.1038/ncb998.

Authors

Natalia Pediconi¹, Alessandra Ianari, Antonio Costanzo, Laura Belloni, Rita Gallo, Letizia Cimino, Antonio Porcellini, Isabella Screpanti, Clara Balsano, Edoardo Alesse, Alberto Gulino, Massimo Levrero

Affiliation

¹ Laboratory of Gene Expression, Fondazione Andrea Cesalpino, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy.

PMID: 12766778
DOI: 10.1038/ncb998

Abstract

E2F1, a member of the E2F family of transcription factors, in addition to its established proliferative effect, has also been implicated in the induction of apoptosis through p53-dependent and p53-independent pathways. 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 damage 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetylation / drug effects
Apoptosis / drug effects
Apoptosis / genetics
Apoptosis / physiology*
Cell Cycle Proteins*
Chromatin / genetics
Chromatin / metabolism
DNA Damage*
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / physiology
Doxorubicin / pharmacology
E2F Transcription Factors
E2F1 Transcription Factor
Etoposide / pharmacology
Fibroblasts
Gene Deletion
Gene Expression Regulation*
Genes, Reporter
Genes, Tumor Suppressor
Histones / analysis
Humans
Nuclear Proteins / genetics*
Nuclear Proteins / physiology
Promoter Regions, Genetic / drug effects
RNA, Messenger / genetics
RNA, Messenger / metabolism
Transcription Factors / metabolism*
Transcriptional Activation
Tumor Cells, Cultured
Tumor Protein p73
Tumor Suppressor Proteins

Substances

Cell Cycle Proteins
Chromatin
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
E2F1 protein, human
Histones
Nuclear Proteins
RNA, Messenger
TP73 protein, human
Transcription Factors
Tumor Protein p73
Tumor Suppressor Proteins
Etoposide
Doxorubicin