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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
08:47

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation

Published on: March 5, 2018

Calpain-1 cleaves and activates caspase-7

Juliette Gafni1, Xin Cong, Sylvia F Chen

  • 1Buck Institute for Age Research, Novato, California 94945, USA.

The Journal of Biological Chemistry
|July 21, 2009
PubMed

Insights

Calpain-1 directly cleaves caspase-7, generating novel, highly active forms. This calpain-activated caspase-7 exhibits unique enzymatic activity and cellular localization, impacting apoptosis and neurodegenerative disease research.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Neuroscience

Background:

  • Caspase-7 is a key executioner caspase in apoptosis, cancer, and neurodegenerative diseases.
  • Its activation by granzyme B and caspase-3 is understood, but regulation by other proteases like calpains remains unclear.

Purpose of the Study:

  • To investigate whether calpains can activate or inactivate caspase-7.
  • To characterize the novel products and enzymatic properties of calpain-cleaved caspase-7.

Main Methods:

  • Recombinant caspase-7 cleavage by calpain-1.
  • Enzymatic activity assays (Vmax, zymography).
  • Mass spectrometry and site-directed mutagenesis for cleavage site identification.
  • In vivo studies in cortical neurons with calcium dysregulation.

Main Results:

  • Calpain-1 directly cleaves caspase-7 at amino acids 36 and 45/47, producing p18 and p17 subunits.
  • The p17 fragment shows an 18-fold increase in activity compared to caspase-3 cleaved products.
  • Calpain-mediated cleavage alters caspase-7's nuclear localization.
  • Calpain-activated caspase-7 exhibits distinct enzymatic activity, localization, and binding affinity.

Conclusions:

  • Calpain-1 is a novel activator of caspase-7, generating highly active forms.
  • Calpain-mediated caspase-7 activation has unique biochemical and cellular properties.
  • This finding provides new insights into caspase-7 regulation in cellular processes like apoptosis and calcium-related neurological conditions.

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