ArticlePloS one2011
Eeyarestatin 1 interferes with both retrograde and anterograde intracellular trafficking pathways.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
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- VDAC1 is a target for pharmacologically induced insulin hypersecretion in β cells.Cell reports · 2025Article
- Is cholesterol both the lock and key to abnormal transmembrane signals in Autism Spectrum Disorder?Lipids in health and disease · 2024Article
- Dual Action of Eeyarestatin 24 on Sec-Dependent Protein Secretion and Bacterial DNA.ACS infectious diseases · 2023Article
- Inhibitors of the Sec61 Complex and Novel High Throughput Screening Strategies to Target the Protein Translocation Pathway.International journal of molecular sciences · 2021Review
- Eeyarestatin 24 impairs SecYEG-dependent protein trafficking and inhibits growth of clinically relevant pathogens.Molecular microbiology · 2021Article
- Natural products as modulators of eukaryotic protein secretion.Natural product reports · 2020Review
- Eeyarestatin Compounds Selectively Enhance Sec61-Mediated CaCell chemical biology · 2019Article
- Human preprocalcitonin self-antigen generates TAP-dependent and -independent epitopes triggering optimised T-cell responses toward immune-escaped tumours.Nature communications · 2018Article
- Inhibitors of protein translocation across membranes of the secretory pathway: novel antimicrobial and anticancer agents.Cellular and molecular life sciences : CMLS · 2018Review
- Article
- Chemical Modulation of Endocytic Sorting Augments Adeno-associated Viral Transduction.The Journal of biological chemistry · 2016Article
- Synthesis of Fluorophores that Target Small Molecules to the Endoplasmic Reticulum of Living Mammalian Cells.Angewandte Chemie (International ed. in English) · 2015Article
- Whole-genome RNAi screen highlights components of the endoplasmic reticulum/Golgi as a source of resistance to immunotoxin-mediated cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Shiga Toxin (Stx) Classification, Structure, and Function.Microbiology spectrum · 2014Review
- TRC40 can deliver short secretory proteins to the Sec61 translocon.Journal of cell science · 2012Article
- Inhibition of protein translocation at the endoplasmic reticulum promotes activation of the unfolded protein response.The Biochemical journal · 2012Article
- Loss of soluble N-ethylmaleimide-sensitive factor attachment protein α (αSNAP) induces epithelial cell apoptosis via down-regulation of Bcl-2 expression and disruption of the Golgi.The Journal of biological chemistry · 2012Article
- Cytosolic entry of Shiga-like toxin a chain from the yeast endoplasmic reticulum requires catalytically active Hrd1p.PloS one · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe small molecule Eeyarestatin I (ESI) inhibits the endoplasmic reticulum (ER)-cytosol dislocation and subsequent degradation of ERAD (ER associated protein degradation) substrates. Toxins such as ricin and Shiga/Shiga-like toxins (SLTx) are endocytosed and trafficked to the ER. Their catalytic subunits are thought to utilise ERAD-like mechanisms to dislocate from the ER into the cytosol, where a proportion uncouples from the ERAD process, recovers a catalytic conformation and destroys their cellular targets. We therefore investigated ESI as a potential inhibitor of toxin dislocation. METHODOLOGY AND PRINCIPAL
findingsUsing cytotoxicity measurements, we found no role for ES(I) as an inhibitor of toxin dislocation from the ER, but instead found that for SLTx, ESI treatment of cells was protective by reducing the rate of toxin delivery to the ER. Microscopy of the trafficking of labelled SLTx and its B chain (lacking the toxic A chain) showed a delay in its accumulation at a peri-nuclear location, confirmed to be the Golgi by examination of SLTx B chain metabolically labelled in the trans-Golgi cisternae. The drug also reduced the rate of endosomal trafficking of diphtheria toxin, which enters the cytosol from acidified endosomes, and delayed the Golgi-specific glycan modifications and eventual plasma membrane appearance of tsO45 VSV-G protein, a classical marker for anterograde trafficking. CONCLUSIONS AND SIGNIFICANCE: ESI acts on one or more components that function during vesicular transport, whilst at least one retrograde trafficking pathway, that of ricin, remains unperturbed.
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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.