Trial reportThe Journal of biological chemistry2012
Cathepsin D primes caspase-8 activation by multiple intra-chain proteolysis.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 57 citations in OpenAlex.
- Small molecule screening identifies cytotoxic endoplasmic reticulum-associated degradation inhibitors in multiple myeloma.Cell death & disease · 2026Article
- It's a Trap!-Potential of Cathepsins in NET Formation.International journal of molecular sciences · 2025Review
- Article
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- ORMDL3‑mediated bronchial epithelial pyroptosis leads to lung inflammation in obese mice with asthma.Molecular medicine reports · 2023Article
- The cardiac wound healing response to myocardial infarction.WIREs mechanisms of disease · 2023Review
- Functional Analysis of the Cathepsin D Gene Response to SGIV Infection in the Orange-Spotted Grouper,Viruses · 2022Article
- LAMP3 inhibits autophagy and contributes to cell death by lysosomal membrane permeabilization.Autophagy · 2022Article
- The Achilles' heel of cancer: targeting tumors via lysosome-induced immunogenic cell death.Cell death & disease · 2022Review
- Autophagy triggers CTSD (cathepsin D) maturation and localization inside cells to promote apoptosis.Autophagy · 2021Article
- Cathepsin S Cleaves BAX as a Novel and Therapeutically Important Regulatory Mechanism for Apoptosis.Pharmaceutics · 2021Article
- Mitophagy Disequilibrium, a Prominent Pathological Mechanism in Metabolic Heart Diseases.Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Review
- Low-density lipoprotein receptor-related protein 6 regulates cardiomyocyte-derived paracrine signaling to ameliorate cardiac fibrosis.Theranostics · 2021Article
- Exophilin-5 Supports Lysosome-Mediated Trafficking Required for Epidermal Differentiation.The Journal of investigative dermatology · 2019Article
- Neutrophil proteome shifts over the myocardial infarction time continuum.Basic research in cardiology · 2019Article
- Lysosomal cathepsin D is upregulated in Alzheimer's disease neocortex and may be a marker for neurofibrillary degeneration.Brain pathology (Zurich, Switzerland) · 2019Article
- Dimerization and auto-processing induce caspase-11 protease activation within the non-canonical inflammasome.Life science alliance · 2018Article
- Human Cytomegalovirus Protein pUL38 Prevents Premature Cell Death by Binding to Ubiquitin-Specific Protease 24 and Regulating Iron Metabolism.Journal of virology · 2018Article
- A novel acridine derivative, LS-1-10 inhibits autophagic degradation and triggers apoptosis in colon cancer cells.Cell death & disease · 2017Article
- Myocardial Upregulation of Cathepsin D by Ischemic Heart Disease Promotes Autophagic Flux and Protects Against Cardiac Remodeling and Heart Failure.Circulation. Heart failure · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. A direct and fast activation of caspase-8 by cathepsin D was shown to be crucial in the initial steps of neutrophil apoptosis. Nevertheless, the activation mechanism of caspase-8 remains unclear. Here, by using site-specific mutants of caspase-8, we show that both cathepsin D-mediated proteolysis and homodimerization of caspase-8 are necessary to generate an active caspase-8. At acidic pH, cathepsin D specifically cleaved caspase-8 but not the initiator caspase-9 or -10 and significantly increased caspase-8 activity in dimerizing conditions. These events were completely abolished by pepstatin A, a pharmacological inhibitor of cathepsin D. The cathepsin D intra-chain proteolysis greatly stabilized the active site of caspase-8. Moreover, the main caspase-8 fragment generated by cathepsin D cleavage could be affinity-labeled with the active site probe biotin-VAD-fluoromethyl ketone, suggesting that this fragment is enzymatically active. Importantly, in an in vitro cell-free assay, the addition of recombinant human caspase-8 protein, pre-cleaved by cathepsin D, was followed by caspase-3 activation. Our data therefore indicate that cathepsin D is able to initiate the caspase cascade by direct activation of caspase-8. As cathepsin D is ubiquitously expressed, this may represent a general mechanism to induce apoptosis in a variety of immune and nonimmune cells.
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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.