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E2F3 contributes both to the inappropriate proliferation and to the apoptosis arising in Rb mutant embryos

U Ziebold1, T Reza, A Caron

  • 1Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Genes & Development
|March 7, 2001
PubMed

Insights

The retinoblastoma protein (pRB) normally suppresses tumors. Loss of pRB causes cell overgrowth and death, but E2F3, not just E2F1, significantly drives this pRB-loss-induced apoptosis.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Genetics

Background:

  • The retinoblastoma protein (pRB) is a crucial tumor suppressor.
  • E2F transcription factors are downstream targets of pRB and regulate cell proliferation.
  • Current understanding suggests E2F1 induces apoptosis, while E2F1, E2F2, and E2F3 activate proliferation.

Purpose of the Study:

  • To investigate the specific roles of E2F transcription factors in apoptosis and proliferation.
  • To clarify the function of E2F3 in the context of pRB loss.
  • To challenge the prevailing model of E2F-mediated apoptosis.

Main Methods:

  • Analysis of Rb mutant embryos.
  • Generation and study of Rb(-/-);E2f3(+/-) compound mutant embryos.
  • Assessment of cellular proliferation and p53-dependent apoptosis.

Main Results:

  • A mutation in E2f3 completely suppressed inappropriate proliferation in Rb mutant embryos.
  • The E2f3 mutation also suppressed p53-dependent apoptosis in Rb mutant embryos.
  • Separation of E2F3's apoptotic and proliferative roles was achieved through compound mutant analysis.

Conclusions:

  • E2F3 plays a significant role in inducing apoptosis following pRB loss.
  • Contrary to prior beliefs, E2F3 contributes substantially to pRB-loss-induced apoptosis.
  • The function of E2F3 extends beyond proliferation to include a major role in programmed cell death.

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