Role for the p53 homologue p73 in E2F-1-induced apoptosis

Nature. 2000 Oct 5;407(6804):645-8. doi: 10.1038/35036614.

Abstract

The transcription factor E2F-1 induces both cell-cycle progression and, in certain settings, apoptosis. E2F-1 uses both p53-dependent and p53-independent pathways to kill cells. The p53-dependent pathway involves the induction by E2F-1 of the human tumour-suppressor protein p14ARF, which neutralizes HDM2 (human homologue of MDM2) and thereby stabilizes the p53 protein. Here we show that E2F-1 induces the transcription of the p53 homologue p73. Disruption of p73 function inhibited E2F-1-induced apoptosis in p53-defective tumour cells and in p53-/- mouse embryo fibroblasts. We conclude that activation of p73 provides a means for E2F-1 to induce death in the absence of p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Line
  • DNA / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Gene Expression Regulation
  • Genes, Tumor Suppressor
  • Mice
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Protein Binding
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / physiology*
  • Transcription, Genetic
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Proteins

Substances

  • Arid4a protein, mouse
  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, mouse
  • Nuclear Proteins
  • Retinoblastoma-Binding Protein 1
  • TP73 protein, human
  • Transcription Factor DP1
  • Transcription Factors
  • Trp73 protein, mouse
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • DNA