Evidence map›Paper›PMID 27935997›Full record

ArticlePloS one2016

Endoplasmic Reticulum-Targeted Subunit Toxins Provide a New Approach to Rescue Misfolded Mutant Proteins and Revert Cell Models of Genetic Diseases.

Humaira Adnan, Zhenbo Zhang, Hyun-Joo Park, Chetankumar Tailor, Clare Che, Mustafa Kamani, George Spitalny, Beth Binnington, Clifford Lingwood

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023
    Review
  3. Review
  4. Review
  5. Article
  6. Verotoxin Receptor-Based Pathology and Therapies.Frontiers in cellular and infection microbiology · 2020
    Review
  7. Review
  8. Review
  9. Review
  10. Review
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

9 authors at 2 institutions in 1 country.

Humaira AdnanDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
Zhenbo ZhangDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
Hyun-Joo ParkDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
Chetankumar TailorDivision of Cell Biology, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada.
Clare CheDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
Mustafa KamaniDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
George SpitalnyERAD Therapeutics, Caledon, Ontario, Canada.
Beth BinningtonDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.
Clifford LingwoodDivision of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada.ORCID http://orcid.org/0000-0001-9096-0061
Hospital for Sick Children · CAUniversity of Toronto · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Many germ line diseases stem from a relatively minor disturbance in mutant protein endoplasmic reticulum (ER) 3D assembly. Chaperones are recruited which, on failure to correct folding, sort the mutant for retrotranslocation and cytosolic proteasomal degradation (ER-associated degradation-ERAD), to initiate/exacerbate deficiency-disease symptoms. Several bacterial (and plant) subunit toxins, retrograde transport to the ER after initial cell surface receptor binding/internalization. The A subunit has evolved to mimic a misfolded protein and hijack the ERAD membrane translocon (dislocon), to effect cytosolic access and cytopathology. We show such toxins compete for ERAD to rescue endogenous misfolded proteins. Cholera toxin or verotoxin (Shiga toxin) containing genetically inactivated (± an N-terminal polyleucine tail) A subunit can, within 2-4 hrs, temporarily increase F508delCFTR protein, the major cystic fibrosis (CF) mutant (5-10x), F508delCFTR Golgi maturation (<10x), cell surface expression (20x) and chloride transport (2x) in F508del CFTR transfected cells and patient-derived F508delCFTR bronchiolar epithelia, without apparent cytopathology. These toxoids also increase glucocerobrosidase (GCC) in N370SGCC Gaucher Disease fibroblasts (3x), another ERAD-exacerbated misfiling disease. We identify a new, potentially benign approach to the treatment of certain genetic protein misfolding diseases.

Indexed as

Blotting, WesternCholera ToxinCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorEndoplasmic ReticulumEndoplasmic Reticulum-Associated DegradationHEK293 CellsHumansMicroscopy, FluorescenceModels, BiologicalMutationProtein FoldingProtein TransportProteostasis DeficienciesShiga ToxinsToxins, BiologicalCholera ToxinCystic Fibrosis Transmembrane Conductance RegulatorShiga ToxinsToxins, Biological

Identifiers

PMID27935997
PMCPMC5147855
OpenAlexW2560760824

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.