E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo

Roderick L. Beijersbergen, Ron M. Kerkhoven, Liang Zhu, Leone Carlée, P. Mathijs Voorhoeve, René Bernards

Research output: Contribution to journalArticle

306 Scopus citations

Abstract

The E2F family of transcription factors controls the expression of genes that are involved in cell cycle regulation. E2F DNA-binding activity is found in complex with the retinoblastoma protein, pRb, and with the pRb-related p107 and p130. To date, cDNAs for three members of the E2F gene family have been isolated. However, all three E2Fs associate in vivo exclusively with pRb. We report here the cloning and functional analysis of a fourth E2F family member. E2F-4 encodes a 413-amino-acid protein with significant homology to E2F-1. E2F-4 antibodies recognize a 60-kD protein in anti-p107 immunoprecipitates, indicating that E2F-4 associates with p107 in vivo. Like the other E2Fs, E2F-4 requires DP-1 for efficient DNA binding and transcriptional activation of E2F site-containing promoters. Increased expression of E2F-4 and DP-1 in SaoS-2 osteosarcoma cells causes a shift from G1-phase cells to S and G2/M-phase cells, suggesting a role for E2F-4 in regulation of cell-cycle progression. We show that expression of E2F-4 and DP-1 together with an activated ras oncogene in rat embryo fibroblasts, causes transformation, indicating that E2F-4 has oncogenic activity.

Original languageEnglish (US)
Pages (from-to)2680-2690
Number of pages11
JournalGenes and Development
Volume8
Issue number22
DOIs
StatePublished - Nov 15 1994

Keywords

  • E2F
  • cell cycle
  • oncogene
  • p107

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo'. Together they form a unique fingerprint.

  • Cite this

    Beijersbergen, R. L., Kerkhoven, R. M., Zhu, L., Carlée, L., Voorhoeve, P. M., & Bernards, R. (1994). E2F-4, a new member of the E2F gene family, has oncogenic activity and associates with p107 in vivo. Genes and Development, 8(22), 2680-2690. https://doi.org/10.1101/gad.8.22.2680