p53 and E2F-1 cooperate to mediate apoptosis

Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3602-6. doi: 10.1073/pnas.91.9.3602.

Abstract

The tumor-suppressor protein p53 appears to function at the G1 phase of the cell cycle as a checkpoint in response to DNA damage. Mutations in the p53 gene lead to an increased rate of genomic instability and tumorigenesis. The E2F-1 transcription factor is a protein partner of the retinoblastoma-susceptibility gene product, RB. E2F-1 appears to function as a positive regulator or signal for entry into S phase. To explore possible interactions of p53 and E2F-1 in the cell cycle, a human E2F-1 expression plasmid was introduced into a murine cell line containing a temperature-sensitive p53 allele which produces a p53 protein in the wild-type conformation at 32 degrees C and the mutant form at 37.5 degrees C. Coexpression of the wild-type p53 protein and E2F-1 in these cells resulted in a rapid loss of cell viability through a process of apoptosis. Thus, the cell cycle utilizes an interacting or communicative pathway between RB-E2F-1 and p53.

Publication types

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

MeSH terms

  • Apoptosis*
  • Base Sequence
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • DNA-Binding Proteins / metabolism
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Molecular Sequence Data
  • Oligodeoxyribonucleotides / chemistry
  • Recombinant Proteins
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors / physiology*
  • Transfection
  • Tumor Suppressor Protein p53 / physiology*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Oligodeoxyribonucleotides
  • Recombinant Proteins
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Protein p53