ArticlePLoS pathogens2014
Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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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.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- The genome of a vestimentiferan tubeworm (Ridgeia piscesae) provides insights into its adaptation to a deep-sea environment.BMC genomics · 2023Article
- Revisiting bacterial cytolethal distending toxin structure and function.Frontiers in cellular and infection microbiology · 2023Article
- Delivery, structure, and function of bacterial genotoxins.Virulence · 2022Review
- Bacterial AB toxins and host-microbe interactions.Advances in microbial physiology · 2022Review
- Bacterial Toxins Are a Never-Ending Source of Surprises: From Natural Born Killers to Negotiators.Toxins · 2021Review
- Derlin-1 Promotes the Progression of Human Hepatocellular Carcinoma via the Activation of AKT Pathway.OncoTargets and therapy · 2020Article
- Internalization and Intoxication of Human Macrophages by the Active Subunit of theFrontiers in immunology · 2020Article
- Review
- Unique features in the intracellular transport of typhoid toxin revealed by a genome-wide screen.PLoS pathogens · 2019Article
- Toxins Utilize the Endoplasmic Reticulum-Associated Protein Degradation Pathway in Their Intoxication Process.International journal of molecular sciences · 2019Review
- Genome-Wide Identification of Host Genes Required for Toxicity of Bacterial Cytolethal Distending Toxin in a Yeast Model.Frontiers in microbiology · 2019Article
- Article
- Article
- Host cell interactions of outer membrane vesicle-associated virulence factors of enterohemorrhagic Escherichia coli O157: Intracellular delivery, trafficking and mechanisms of cell injury.PLoS pathogens · 2017Article
- Internalization of the Active Subunit of theFrontiers in cellular and infection microbiology · 2017Article
- Intracellular trafficking of bacterial toxins.Current opinion in cell biology · 2016Review
- Review
- Review
- Molecular Mechanisms and Potential Clinical Applications of Campylobacter jejuni Cytolethal Distending Toxin.Frontiers in cellular and infection microbiology · 2016Review
- The Cytolethal Distending Toxin Contributes to Microbial Virulence and Disease Pathogenesis by Acting As a Tri-Perditious Toxin.Frontiers in cellular and infection microbiology · 2016Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.
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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.