ArticleCell death discovery2019
The prodomain of caspase-3 regulates its own removal and caspase activation.
Article in Cell death discovery, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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Who cites it
73 citing papers in PubMed.
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- Human non-canonical inflammasomes activate CASP3 to limit intracellular Salmonella replication in macrophages.PLoS pathogens · 2026Article
- Ectopic expression of a human cysteine aspartate-specific protease genePlant biotechnology (Tokyo, Japan) · 2026Article
- Pharmacologic Modulation of the PAR-2-ERK Axis by Statins Converts Inflammatory Survival Signalling into Apoptosis in Colorectal Cancer Cells.International journal of molecular sciences · 2026Article
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- Mimulone-induced Apoptosis through the Extrinsic Pathway and ERK Inactivation in Human Hepatoma Hep3B Cells.Cell biochemistry and biophysics · 2025Article
- Neurotoxicity Assessment of Perfluoroundecanoic Acid (PFUnDA) in Developing Zebrafish (Toxics · 2025Article
- Human non-canonical inflammasomes activate CASP3 to limit intracellularbioRxiv : the preprint server for biology · 2025Article
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- Caspase-14-like Proteases: An Epidermal Caspase and Its Evolutionarily Ancient Relatives.Biomolecules · 2025Review
- PF-06447475 Molecule Attenuates the Neuropathology of Familial Alzheimer's and Coexistent Parkinson's Disease Markers in PSEN1 I416T Dopaminergic-like Neurons.Molecules (Basel, Switzerland) · 2025Article
- Applying Ultrasound to Mechanically and Noninvasively Sensitize Prostate Tumors to TRAIL-Mediated Apoptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Caspase 3 and caspase 7 promote cytoprotective autophagy and the DNA damage response during non-lethal stress conditions in human breast cancer cells.PLoS biology · 2025Article
- Consumption of Endogenous Caspase-3 Activates Molecular Theranostic Nanoplatform against Inflammation-Induced Profibrotic Positive Feedback in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Effects of Nicotinamide Riboside Supplementation on Postmortem Mitochondrial Functionality and Apoptotic Activation.Metabolites · 2025Article
- Design, synthesis,Frontiers in chemistry · 2025Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Caspase-3 is a cysteine-aspartic acid protease that cleaves cellular targets and executes cell death. Our current understanding is caspase-3 is activated by the cleavage of the interdomain linker and then subsequent cleavage of the N-terminal prodomain. However, previous reports have suggested that removal of the prodomain can result in the constitutive activation of caspase-3, although other studies have not observed this. To address this question in a more physiological setting, we developed an inducible doxycycline system to express a mutant form of caspase-3 that lacks the prodomain (∆28). We found that the removal of the prodomain renders the cells more susceptible to death signals, but the caspase is not constitutively active. To elucidate the regions of the prodomain that regulate activity, we created deletion constructs that remove 10 and 19 N-terminal amino acids. Surprisingly, removal of the first 10 amino acids renders caspase-3 inactive. Following serum withdrawal, the interdomain linker is cleaved, however, the remaining prodomain is not removed. Therefore, there is a specific amino acid or stretch of amino acids within the first 10 that are important for prodomain removal and caspase-3 function. We created different point mutations within the prodomain and found amino acid D9 is vital for caspase-3 function. We hypothesize that an initial cleavage event at D9 is required to allow cleavage at D28 that causes the complete removal of the prodomain allowing for full caspase activation. Together these findings demonstrate a previously unknown role of the prodomain in caspase activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.