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Updated: May 11, 2026

Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
Murine caspase-11, an ICE-interacting protease, is essential for the activation of ICE
1Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Abstract:
We report here the inactivation of a member of the Ice/Ced-3 (caspase) family of cell death genes, casp-11, by gene targeting. Like Ice-deficient mice, casp-11 mutant mice are resistant to endotoxic shock induced by lipopolysaccharide. Production of both IL-1alpha and IL-1beta after lipopolysaccharide stimulation, a crucial event during septic shock and an indication of ICE activation, is blocked in casp-11 mutant mice. casp-11 mutant embryonic fibroblast cells are resistant to apoptosis induced by overexpression of ICE. Furthermore, we found that pro-caspase-11 physically interacts with pro-ICE in cells, and the expression of casp-11 is essential for activation of ICE. Our data suggest that caspase-11 is a component of ICE complex and is required for the activation of ICE.
Insights
Caspase-11 (casp-11) gene inactivation renders mice resistant to endotoxic shock. Caspase-11 is essential for Interleukin-1 converting enzyme (ICE) activation, suggesting it
Area of Science:
- Molecular Biology
- Immunology
- Cell Death Research
Background:
- The Ice/Ced-3 (caspase) gene family plays a critical role in programmed cell death.
- Interleukin-1 converting enzyme (ICE) activation is a key event in inflammatory responses like septic shock.
Purpose of the Study:
- To investigate the role of caspase-11 (casp-11) in cell death pathways and inflammatory responses.
- To determine if casp-11 is involved in the activation of ICE.
Main Methods:
- Gene targeting to create casp-11 mutant mice.
- Analysis of endotoxic shock resistance in mutant mice.
- Assessment of IL-1alpha and IL-1beta production following lipopolysaccharide stimulation.
- Apoptosis assays using casp-11 mutant embryonic fibroblast cells.
- Co-immunoprecipitation to study protein interactions between pro-caspase-11 and pro-ICE.
Main Results:
- Casp-11 mutant mice exhibit resistance to lipopolysaccharide-induced endotoxic shock.
- Production of IL-1alpha and IL-1beta is blocked in casp-11 mutant mice after lipopolysaccharide stimulation.
- Casp-11 mutant cells are resistant to apoptosis induced by ICE overexpression.
- Pro-caspase-11 physically interacts with pro-ICE in cells.
- Caspase-11 expression is crucial for ICE activation.
Conclusions:
- Caspase-11 is a necessary component of the ICE complex.
- Caspase-11 is required for the activation of ICE, playing a vital role in inflammatory signaling and cell death.
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