E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis

T. F. Kowalik, J. DeGregori, J. K. Schwarz, J. R. Nevins

Research output: Contribution to journalArticle

364 Citations (Scopus)

Abstract

Various experiments have demonstrated a role for the E2F transcription factor in the regulation of cell growth during the G0/G1/S phase transition. Indeed, overexpression of the E2F1 product, a component of the cellular E2F activity, induces DNA synthesis in quiescent fibroblasts. To provide an approach to a more detailed biochemical analysis of these events, we have made use of a recombinant adenovirus containing the E2F1 cDNA in order to efficiently express the E2F1 product in an entire population of cells. We demonstrate an induction of DNA synthesis when quiescent cells are infected with the E2F1 recombinant virus. However, we also find that the induction does not lead to a complete replication of the cellular genome, as revealed by flow cytometry. The incomplete nature of cellular DNA replication is due, at least in part, to the fact that E2F1 overexpression leads to massive cell death that is characteristic of apoptosis. This E2F1-mediated induction of apoptosis is largely dependent on endogenous wild-type p53 activity and can be subverted by introducing mutant forms of p53 into these cells or by overexpressing E2F1 in fibroblasts derived from p53-null mouse embryos. We conclude that E2F1 can induce events leading to S phase but that the process is not normal and appears to result from the activation of a cell death pathway.

Original languageEnglish (US)
Pages (from-to)2491-2500
Number of pages10
JournalJournal of virology
Volume69
Issue number4
StatePublished - Jan 1 1995

Fingerprint

fibroblasts
apoptosis
Fibroblasts
Apoptosis
interphase
synthesis
cell death
DNA
S Phase
Cell Death
E2F Transcription Factors
Adenoviridae
DNA replication
cells
phase transition
flow cytometry
cell growth
Phase Transition
G1 Phase
transcription factors

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. / Kowalik, T. F.; DeGregori, J.; Schwarz, J. K.; Nevins, J. R.

In: Journal of virology, Vol. 69, No. 4, 01.01.1995, p. 2491-2500.

Research output: Contribution to journalArticle

Kowalik, T. F. ; DeGregori, J. ; Schwarz, J. K. ; Nevins, J. R. / E2F1 overexpression in quiescent fibroblasts leads to induction of cellular DNA synthesis and apoptosis. In: Journal of virology. 1995 ; Vol. 69, No. 4. pp. 2491-2500.
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