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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
07:42

Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c

Published on: June 29, 2011

c-Myc functionally cooperates with Bax to induce apoptosis

Philippe Juin1, Abigail Hunt, Trevor Littlewood

  • 1University of California at San Francisco Cancer Center, San Francisco, California 94143-0128, USA.

Molecular and Cellular Biology
|August 9, 2002
PubMed

Insights

The oncogene c-Myc induces programmed cell death (apoptosis) by disrupting mitochondria. This process requires the protein Bax, but c-Myc does not alter Bax levels, suggesting an indirect mechanism.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Biochemistry

Background:

  • c-Myc is a transcription factor known to regulate cell proliferation, differentiation, and apoptosis.
  • Mitochondrial integrity is crucial for regulating cell death pathways, with proteins like Bcl-2 family members playing key roles.
  • The precise mechanisms by which c-Myc induces apoptosis, particularly its interaction with the Bcl-2 family, are not fully understood.

Purpose of the Study:

  • To elucidate the role of Bcl-2 family proteins, specifically Bax and Bak, in c-Myc-induced apoptosis.
  • To investigate how c-Myc activation influences Bax expression, localization, and conformation.
  • To determine if direct activation of proapoptotic pathways can rescue c-Myc-induced apoptosis in resistant cells.

Main Methods:

  • Utilized knockout fibroblasts lacking Bak or Bax to assess susceptibility to c-Myc-induced apoptosis.
  • Analyzed Bax expression, localization, and conformation following c-Myc activation.
  • Employed ectopic expression of Bax and microinjection of a BH3-only domain peptide to restore apoptosis sensitivity.
  • Examined the synergistic effects of BH3 peptide and c-Myc in cells with varying Bax and Bak deficiencies.

Main Results:

  • Fibroblasts lacking Bak remained susceptible to c-Myc-induced apoptosis, while those lacking Bax were resistant.
  • c-Myc activation did not alter Bax expression, localization, or conformation.
  • Ectopic Bax expression or BH3 peptide microinjection restored c-Myc sensitivity in Bax-deficient cells.
  • BH3 peptide also restored sensitivity in p53-deficient cells, but not in cells lacking both Bax and Bak.

Conclusions:

  • c-Myc induces apoptosis through a mechanism that requires Bax but does not involve changes in Bax expression or conformation.
  • c-Myc triggers a mitochondrial destabilizing activity that cooperates with proapoptotic Bcl-2 family members.
  • Direct activation of BH3-only domains can bypass certain resistance mechanisms to c-Myc-induced apoptosis.

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