Overexpression of E2F-1 in rat embryo fibroblasts leads to neoplastic transformation

EMBO J. 1994 Jul 15;13(14):3329-38.

Abstract

The transcription factor E2F has been implicated in controlling the activation of multiple genes associated with cell proliferation. E2F-1, which is a component of E2F, can promote oncogenesis when transfected into REF cells. The transformation caused by E2F-1 correlates with constitutive overexpression of the transgene, increased transcription of E2F-dependent genes and the enhancement of two E2F DNA binding complexes containing the retinoblastoma susceptibility gene product (Rb) and E2F-1. The oncogenic potential of E2F-1 is dependent on functional DNA binding and transactivation domains but does not require the ability to interact directly with Rb. These findings provide the first direct evidence that sustained unregulated expression of E2F-1 can lead to the loss of cell proliferation control and that E2F-1 is a key component in cell cycle control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins*
  • Cell Cycle Proteins*
  • Cell Transformation, Neoplastic / genetics*
  • Cells, Cultured
  • DNA, Neoplasm / metabolism
  • DNA-Binding Proteins*
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Fibroblasts / physiology*
  • Gene Expression Regulation, Neoplastic*
  • Neoplasms, Experimental
  • Protein Binding
  • Protein Biosynthesis
  • Protein Conformation
  • Rats
  • Recombinant Proteins / biosynthesis
  • Retinoblastoma Protein / metabolism
  • Retinoblastoma-Binding Protein 1
  • Structure-Activity Relationship
  • Transcription Factor DP1
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Transcription, Genetic
  • Transfection

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • DNA, Neoplasm
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2f1 protein, rat
  • Recombinant Proteins
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • Transcription Factor DP1
  • Transcription Factors