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Updated: Dec 23, 2025
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Lighting Up the Pathways to Caspase Activation Using Bimolecular Fluorescence Complementation
Published on: March 5, 2018
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Non-Canonical Caspase Activity Antagonizes p38 MAPK Stress-Priming Function to Support Development.
Benjamin P Weaver1, Yi M Weaver1, Shizue Omi2
1Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder and Howard Hughes Medical Institute, Boulder, CO 80309, USA.
Developmental Cell
|April 18, 2020
Summary
The CED-3 caspase limits stress responses to promote larval development in C. elegans by cleaving the PMK-1 pathway. This balance is crucial for regulating gene expression during development.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Apoptotic caspases exhibit non-canonical functions, including gene expression modulation.
- Caspases can limit stem cell divisions and influence developmental processes.
Purpose of the Study:
- To investigate the non-canonical role of CED-3 caspase in regulating C. elegans larval development.
- To elucidate the interaction between CED-3 caspase and the PMK-1 stress-responsive pathway.
Main Methods:
- Analysis of gene expression changes regulated by CED-3 and PMK-1.
- Biochemical assays to determine direct cleavage of PMK-1 by CED-3.
- Phenotypic analysis of C. elegans development under varying stress conditions.
Main Results:
- CED-3 caspase directly cleaves and inhibits the PMK-1 (p38 MAPK) pathway.
- PMK-1 activation primes C. elegans for stress but retards development.
- Over 300 genes, including stress-response factors like FASN-1, are inversely regulated by CED-3 and PMK-1.
Conclusions:
- CED-3 promotes development by suppressing epidermal stress responses.
- A balance between CED-3 and PMK-1 is essential for coordinating developmental and stress-related gene expression programs.
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