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Oncogene-dependent apoptosis is mediated by caspase-9

H O Fearnhead1, J Rodriguez, E E Govek

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

Proceedings of the National Academy of Sciences of the United States of America
|November 13, 1998
PubMed

Insights

Oncogenic transformation sensitizes cells to apoptosis by facilitating caspase-9 activation. This process, involving cytochrome c release, offers a potential strategy for selectively killing tumor cells.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Biochemistry

Background:

  • Oncogenic transformation can alter cellular apoptosis pathways.
  • Understanding these alterations may lead to targeted cancer therapies.
  • A cell-free system was previously established to study oncogene-dependent apoptosis.

Purpose of the Study:

  • To investigate the molecular mechanisms by which oncogenes sensitize cells to apoptosis.
  • To validate the role of the caspase-9, Apaf-1, and cytochrome c complex in oncogene-induced apoptosis.

Main Methods:

  • Utilized a cell-free system to study apoptosis.
  • Examined the role of the caspase-9 activation complex.
  • Investigated the effect of E1A, an adenoviral oncogene, on apoptosis and caspase-9 activation.
  • Assessed cytochrome c release from mitochondria.

Main Results:

  • Oncogene-dependent apoptosis requires the caspase-9, Apaf-1, and cytochrome c complex.
  • Inhibition of caspase-9 activation blocked drug-induced apoptosis in E1A-sensitized cells.
  • Oncogenes like E1A facilitate caspase-9 activation, partly through controlling cytochrome c release.

Conclusions:

  • The caspase-9 activation complex is crucial for oncogene-sensitized apoptosis.
  • Targeting caspase-9 activation presents a potential therapeutic strategy for cancers driven by oncogenes.
  • Oncogenes modulate mitochondrial pathways to promote apoptosis.

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