Direct coupling of the cell cycle and cell death machinery by E2F

Nat Cell Biol. 2002 Nov;4(11):859-64. doi: 10.1038/ncb868.


Unrestrained E2F activity forces S phase entry and promotes apoptosis through p53-dependent and -independent mechanisms. Here, we show that deregulation of E2F by adenovirus E1A, loss of Rb or enforced E2F-1 expression results in the accumulation of caspase proenzymes through a direct transcriptional mechanism. Increased caspase levels seem to potentiate cell death in the presence of p53-generated signals that trigger caspase activation. Our results demonstrate that mitogenic oncogenes engage a tumour suppressor network that functions at multiple levels to efficiently induce cell death. The data also underscore how cell cycle progression can be coupled to the apoptotic machinery.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1A Proteins / metabolism
  • Animals
  • Apoptosis*
  • Blotting, Northern
  • Caspases / genetics
  • Caspases / metabolism
  • Cell Cycle
  • Cell Cycle Proteins*
  • Cell Line, Tumor
  • CpG Islands
  • Cytochromes c / metabolism
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Fibroblasts / metabolism
  • Humans
  • Luciferases / metabolism
  • Mice
  • Models, Biological
  • Models, Genetic
  • Promoter Regions, Genetic
  • RNA / chemistry
  • Retinoblastoma Protein / metabolism
  • Time Factors
  • Transcription Factors / chemistry*
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / metabolism


  • Adenovirus E1A Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • Retinoblastoma Protein
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • RNA
  • Cytochromes c
  • Luciferases
  • Caspases