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Updated: Jun 21, 2026
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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
Summary
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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