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Bcl-2 expression in neural cells blocks activation of ICE/CED-3 family proteases during apoptosis

A Srinivasan1, L M Foster, M P Testa

  • 1Program on Aging, Burnham Institute, La Jolla, California 92037, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|September 15, 1996
PubMed

Insights

Bcl-2 protein inhibits programmed cell death by preventing the activation of ICE/CED-3 proteases, crucial enzymes in apoptosis. This occurs upstream of protease activation, without affecting protease gene expression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Programmed cell death, or apoptosis, is regulated by proteases.
  • The ICE/CED-3 family of proteases plays a key role in apoptosis.
  • The mechanism by which Bcl-2 protein represses apoptosis is not fully understood.

Purpose of the Study:

  • To investigate the biochemical mechanism of Bcl-2's anti-apoptotic action.
  • To determine if Bcl-2 affects the activation of ICE/CED-3 proteases during apoptosis.

Main Methods:

  • Used GT1-7 neuronal cells and HeLa cells overexpressing Bcl-2.
  • Induced apoptosis using staurosporine, ceramide, and serum withdrawal.
  • Assessed ICE/CED-3 protease activation via affinity-labeling and fluorogenic substrate assays.
  • Examined nuclear morphological changes in a cell-free system.
  • Analyzed mRNA expression of ICE/CED-3 family members.

Main Results:

  • Apoptotic stimuli activated a 17 kDa subunit of ICE/CED-3-like proteases.
  • This activation correlated with increased protease activity and induction of apoptosis.
  • Overexpressed Bcl-2 inhibited protease activation and apoptosis induction.
  • Bcl-2 did not alter mRNA levels of ICE/CED-3 family members.
  • Bcl-2 prevented the processing of pro-Nedd 2 to its active form.

Conclusions:

  • Bcl-2 acts upstream of ICE/CED-3 protease activation.
  • Bcl-2 inhibits apoptosis by preventing the post-translational activation of ICE/CED-3 proteases.

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