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Related Experiment Videos

Caspase-9 can be activated without proteolytic processing.

H R Stennicke1, Q L Deveraux, E W Humke

  • 1The Program for Apoptosis and Cell Death Research, The Burnham Institute, La Jolla, California 92037, USA.

The Journal of Biological Chemistry
|March 20, 1999
PubMed
Summary
This summary is machine-generated.

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Recombinant procaspase-9 requires cytosolic factors for activation, not just proteolytic processing. This finding reveals context-dependent caspase-9 activity crucial for apoptosis regulation.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Proapoptotic caspase-9 is crucial for programmed cell death.
  • Its activation mechanism is traditionally thought to involve proteolytic processing.

Purpose of the Study:

  • To investigate the context-dependent activation of caspase-9.
  • To determine if proteolytic processing is essential for caspase-9 activity.

Main Methods:

  • Produced recombinant procaspase-9 with mutations disabling interdomain processing sites.
  • Assessed caspase-9 activity in cytosolic extracts of human 293 cells.
  • Evaluated apoptosis support via transient expression in 293 cells.

Main Results:

  • Recombinant caspase-9 is largely inactive when purified but highly activated (2000-fold) by cytosolic factors, cytochrome c, and dATP.

Related Experiment Videos

  • Mutant procaspase-9 forms lacking processing sites activated downstream caspases in a cytosolic factor-dependent manner.
  • A double-mutant procaspase-9 retained significant activity and supported apoptosis, similar to wild-type.

    • Conclusions:

    • Caspase-9 activation is unusually dependent on cytosolic factors rather than solely proteolytic processing.
    • The procaspase-9 zymogen possesses inherent activity modulated by cellular context.
    • This highlights a non-conventional caspase activation pathway essential for apoptosis.