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.

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
  • Transcription Factors
  • Tumor Protein p73
  • Tumor Suppressor Proteins
  • p73 protein, human
  • Etoposide
  • Doxorubicin