ArticleProceedings of the National Academy of Sciences of the United States of America2019
Anthrax toxin requires ZDHHC5-mediated palmitoylation of its surface-processing host enzymes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 33 citations in OpenAlex.
- ZDHHC5: a pivotal palmitoyltransferase orchestrating signaling networks - unraveling mechanisms and therapeutic horizons.Biomarker research · 2026Review
- Metabolism-driven posttranslational modifications and immune regulation: Emerging targets for immunotherapy.Science advances · 2025Review
- Recent advances in S-palmitoylation and its emerging roles in human diseases.Journal of hematology & oncology · 2025Review
- The Biology and Clinical Implications of PCSK7.Endocrine reviews · 2025Review
- Palmitoylation regulates myelination by modulating the ZDHHC3-Cadm4 axis in the central nervous system.Signal transduction and targeted therapy · 2024Article
- Clusters of lineage-specific genes are anchored by ZNF274 in repressive perinucleolar compartments.Science advances · 2024Article
- Review
- Protein acylation by saturated very long chain fatty acids and endocytosis are involved in necroptosis.Cell chemical biology · 2021Article
- Spike glycoprotein and host cell determinants of SARS-CoV-2 entry and cytopathic effects.Journal of virology · 2021Article
- Protein S-Palmitoylation and Lung Diseases.Advances in experimental medicine and biology · 2021Article
- Putative Role of Protein Palmitoylation in Cardiac Lipid-Induced Insulin Resistance.International journal of molecular sciences · 2020Review
- Role of the early secretory pathway in SARS-CoV-2 infection.The Journal of cell biology · 2020Review
- Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase.Communications biology · 2020Article
- Mammalian membrane trafficking as seen through the lens of bacterial toxins.Cellular microbiology · 2020Review
- A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.bioRxiv : the preprint server for biology · 2020Article
- Flotillins: At the Intersection of ProteinInternational journal of molecular sciences · 2020Review
- The motif EThe Journal of biological chemistry · 2020Article
- Novel Targets of SARS-CoV-2 Spike Protein in Human Fetal Brain Development Suggest Early Pregnancy Vulnerability.Frontiers in neuroscience · 2020Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The protein acyl transferase ZDHHC5 was recently proposed to regulate trafficking in the endocytic pathway. Therefore, we explored the function of this enzyme in controlling the action of bacterial toxins. We found that ZDHHC5 activity is required for two very different toxins: the anthrax lethal toxin and the pore-forming toxin aerolysin. Both of these toxins have precursor forms, the protoxins, which can use the proprotein convertases Furin and PC7 for activation. We show that ZDHHC5 indeed affects the processing of the protoxins to their active forms. We found that Furin and PC7 can both be S-palmitoylated and are substrates of ZDHHC5. The impact of ZDHHC5 on Furin/PC7-mediated anthrax toxin cleavage is dual, having an indirect and a direct component. First, ZDHHC5 affects the homeostasis and trafficking of a subset of cellular proteins, including Furin and PC7, presumably by affecting the endocytic/recycling pathway. Second, while not inhibiting the protease activity per se, ZDHHC5-mediated Furin/PC7 palmitoylation is required for the cleavage of the anthrax toxin. Finally, we show that palmitoylation of Furin and PC7 promotes their association with plasma membrane microdomains. Both the receptor-bound toxin and the convertases are of very low abundance at the cell surface. Their encounter is unlikely on reasonable time scales. This work indicates that palmitoylation drives their encounter in specific domains, allowing processing and thereby intoxication of the cell.
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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.