Evidence map›Paper›PMID 28377614›Full record

ArticleScientific reports2017

The Hsp90 machinery facilitates the transport of diphtheria toxin into human cells.

Manuel Schuster, Leonie Schnell, Peter Feigl, Carina Birkhofer, Katharina Mohr, Maurice Roeder, Stefan Carle, Simon Langer, Franziska Tippel, Johannes Buchner and 7 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Domperidone InhibitsToxins · 2023
    Article
  6. Article
  7. Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Proline Isomerization as a Key Determinant for Hsp90-Toxin Interactions.Frontiers in cellular and infection microbiology · 2021
    Article
  13. International journal of molecular sciences · 2020
    Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 6 institutions in 1 country.

Manuel SchusterInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Leonie SchnellInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Peter FeiglInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Carina BirkhoferInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Katharina MohrInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Maurice RoederInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Stefan CarleInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Simon LangerInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany.
Franziska TippelMunich Center for Integrated Protein Science and Department Chemistry, Technical University of Munich, Munich, Germany.
Johannes BuchnerMunich Center for Integrated Protein Science and Department Chemistry, Technical University of Munich, Munich, Germany.
Gunter FischerMax Planck Research Unit for Enzymology of Protein Folding Halle, Halle, Saale, Germany.
Felix HauschInstitute for Organic Chemistry and Biochemistry, Technical University Darmstadt, Darmstadt, Germany.
Manfred FrickInstitute of General Physiology, University of Ulm, Ulm, Germany.ORCID http://orcid.org/0000-0002-4763-1104
Carsten SchwanInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104, Freiburg, Germany.
Klaus AktoriesInstitute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79104, Freiburg, Germany.
Cordelia Schiene-FischerInstitute for Biochemistry and Biotechnology, Martin Luther University Halle-Wittenberg, Halle, Saale, Germany.
Holger BarthInstitute of Pharmacology and Toxicology, University of Ulm Medical Center, Ulm, Germany. holger.barth@uni-ulm.de.
Universität Ulm · DECenter for Integrated Protein Science Munich · DEUniversity of Freiburg · DEMartin Luther University Halle-Wittenberg · DEMax Planck Institute of Psychiatry · DEMax Planck Research Unit for Enzymology of Protein Folding · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Diphtheria toxin kills human cells because it delivers its enzyme domain DTA into their cytosol where it inhibits protein synthesis. After receptor-mediated uptake of the toxin, DTA translocates from acidic endosomes into the cytosol, which might be assisted by host cell factors. Here we investigated the role of Hsp90 and its co-chaperones during the uptake of native diphtheria toxin into human cells and identified the components of the Hsp90 machinery including Hsp90, Hsp70, Cyp40 and the FK506 binding proteins FKBP51 and FKBP52 as DTA binding partners. Moreover, pharmacological inhibition of the chaperone activity of Hsp90 and Hsp70 and of the peptidyl-prolyl cis/trans isomerase (PPIase) activity of Cyps and FKBPs protected cells from intoxication with diphtheria toxin and inhibited the pH-dependent trans-membrane transport of DTA into the cytosol. In conclusion, these host cell factors facilitate toxin uptake into human cells, which might lead to development of novel therapeutic strategies against diphtheria.

Indexed as

AnimalsCarrier ProteinsCell MembraneCells, CulturedCHO CellsCricetulusCytosolDiphtheria ToxinEnzyme ActivationHeLa CellsHost-Pathogen InteractionsHSP90 Heat-Shock ProteinsHumansHydrogen-Ion ConcentrationModels, BiologicalMolecular ChaperonesCarrier ProteinsDiphtheria ToxinHSP90 Heat-Shock ProteinsMolecular ChaperonesPeptidylprolyl Isomerase

Identifiers

PMID28377614
PMCPMC5429619
OpenAlexW2602618603

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.