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Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition

M S Soengas1, R M Alarcón, H Yoshida

  • 1Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.

Science (New York, N.Y.)
|April 2, 1999
PubMed

Insights

The tumor suppressor p53 relies on caspase-9 and Apaf-1 for apoptosis induction. Loss of these proteins, like p53, promotes cancer by enabling oncogene-driven cell survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Death Pathways

Background:

  • The tumor suppressor protein p53 plays a crucial role in preventing cancer by inducing apoptosis in response to oncogenic stress.
  • Understanding the downstream effectors of p53-mediated apoptosis is essential for comprehending tumor suppression mechanisms.

Purpose of the Study:

  • To investigate the role of caspase-9 and Apaf-1 as downstream mediators of p53's tumor suppressor function, particularly in Myc-induced apoptosis.
  • To determine if Apaf-1 and caspase-9 are critical for preventing oncogene-induced cell proliferation and transformation.

Main Methods:

  • Utilized mouse embryo fibroblast (MEF) cells with deficiencies in p53, Apaf-1, and caspase-9.
  • Expressed the oncogene c-Myc in these cell lines to study apoptosis resistance and oncogenic transformation.
  • Assessed cellular responses to apoptotic stimuli under conditions mimicking tumor development.

Main Results:

  • MEF cells lacking p53, or deficient in Apaf-1 and caspase-9, exhibited resistance to Myc-induced apoptosis.
  • Inactivation of Apaf-1 or caspase-9 functionally substituted for p53 loss, promoting oncogenic transformation in Myc-expressing cells.
  • These findings highlight the critical involvement of the Apaf-1/caspase-9 pathway in p53-mediated tumor suppression.

Conclusions:

  • Apaf-1 and caspase-9 are essential downstream components of p53's apoptotic pathway, crucial for tumor suppression.
  • The Apaf-1/caspase-9 axis plays a significant role in controlling tumor development by regulating apoptosis in response to oncogenic signals.

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