ArticleCellular microbiology2011
Role of CypA and Hsp90 in membrane translocation mediated by anthrax protective antigen.
Article in Cellular microbiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 65 citations in OpenAlex.
- Host cyclophilin-mediated maturation of an obligate intracellular bacterial surface virulence factor.bioRxiv : the preprint server for biology · 2025Article
- All-Trans Retinoic Acid-Induced Cell Surface Heat Shock Protein 90 Mediates Tau Protein Internalization and Degradation in Human Microglia.Molecular neurobiology · 2025Article
- The Chaperonin TRiC/CCT Inhibitor HSF1A Protects Cells from Intoxication with Pertussis Toxin.Toxins · 2024Article
- Domperidone InhibitsToxins · 2023Article
- Domperidone Protects Cells from Intoxication withToxins · 2023Article
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- Requirement of Peptidyl-Prolyl Cis/Trans isomerases and chaperones for cellular uptake of bacterial AB-type toxins.Frontiers in cellular and infection microbiology · 2022Review
- Anthrax toxin translocation complex reveals insight into the lethal factor unfolding and refolding mechanism.Scientific reports · 2021Article
- Intoxication of mammalian cells with binary clostridial enterotoxins is inhibited by the combination of pharmacological chaperone inhibitors.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- A High-Affinity Calmodulin-Binding Site in the CyaA Toxin Translocation Domain is Essential for Invasion of Eukaryotic Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- Pharmacological targeting of host chaperones protects from pertussis toxin in vitro and in vivo.Scientific reports · 2021Article
- Cyclophilin A: a key player for etiological agent infection.Applied microbiology and biotechnology · 2021Review
- Proline Isomerization as a Key Determinant for Hsp90-Toxin Interactions.Frontiers in cellular and infection microbiology · 2021Article
- A binding motif for Hsp90 in the A chains of ADP-ribosylating toxins that move from the endoplasmic reticulum to the cytosol.Cellular microbiology · 2019Article
- HSC70 and HSP90 chaperones perform complementary roles in translocation of the cholera toxin A1 subunit from the endoplasmic reticulum to the cytosol.The Journal of biological chemistry · 2019Article
- Involvement of Hsp90 and cyclophilins in intoxication by AIP56, a metalloprotease toxin from Photobacterium damselae subsp. piscicida.Scientific reports · 2019Article
- Review
- Article
- Combined Pharmacological Inhibition of Cyclophilins, FK506-Binding Proteins, Hsp90, and Hsp70 Protects Cells FromFrontiers in pharmacology · 2018Article
- Hsp70 facilitates trans-membrane transport of bacterial ADP-ribosylating toxins into the cytosol of mammalian cells.Scientific reports · 2017Article
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Bacillus anthracis lethal toxin consists of the protective antigen (PA) and the metalloprotease lethal factor (LF). During cellular uptake PA forms pores in membranes of endosomes, and unfolded LF translocates through the pores into the cytosol. We have investigated whether host cell chaperones facilitate translocation of LF and the fusion protein LF(N)DTA. LF(N) mediates uptake of LF(N)DTA into the cytosol, where DTA, the catalytic domain of diphtheria toxin, ADP-ribosylates elongation factor-2, allowing for detection of small amounts of translocated LF(N)DTA. Cyclosporin A, which inhibits peptidyl-prolyl cis/trans isomerase activity of cyclophilins, and radicicol, which inhibits Hsp90 activity, prevented uptake of LF(N)DTA into the cytosol of CHO-K1 cells and protected cells from intoxication by LF(N)DTA/PA. Both inhibitors, as well as an antibody against cyclophilin A blocked the release of active LF(N)DTA from endosomal vesicles into the cytosol in vitro. In contrast, the inhibitors did not inhibit cellular uptake of LF. In vitro, cyclophilin A and Hsp90 bound to LF(N)DTA and DTA but not to LF, implying that DTA determines this interaction. In conclusion, cyclophilin A and Hsp90 facilitate translocation of LF(N)DTA, but not of LF, across endosomal membranes, and thus they function selectively in promoting translocation of certain proteins, but not of others.
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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.