ArticleToxins2014
Direct activation of ribosome-associated double-stranded RNA-dependent protein kinase (PKR) by deoxynivalenol, anisomycin and ricin: a new model for ribotoxic stress response induction.
Article in Toxins, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
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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.
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.
Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Research progress on the toxicological characteristics and biodegradation of deoxynivalenol and its derivatives.Archives of toxicology · 2026Review
- Impacts of trichothecene mycotoxins on human colonic epithelial cells: molecular mechanisms and signaling pathways.Journal of advanced research · 2026Review
- Leveraging Xenobiotic-Responsive Cancer Stemness in Cell Line-Based Tumoroids for Evaluating Chemoresistance: A Proof-of-Concept Study on Environmental Susceptibility.International journal of molecular sciences · 2024Article
- Deoxynivalenol triggers the expression of IL-8-related signaling cascades and decreases protein biosynthesis in primary monocyte-derived cells.Mycotoxin research · 2024Article
- Stress-responsive Gdf15 counteracts renointestinal toxicity via autophagic and microbiota reprogramming.Communications biology · 2023Article
- Lactoferrin Restores the Deoxynivalenol-Impaired Spermatogenesis and Blood-Testis Barrier Integrity via Improving the Antioxidant Capacity and Modifying the Cell Adhesion and Inflammatory Response.Antioxidants (Basel, Switzerland) · 2023Article
- The mycotoxin deoxynivalenol (DON) can deteriorate vaccination efficacy against porcine reproductive and respiratory syndrome virus (PRRSV) at subtoxic levels.Porcine health management · 2022Article
- Interindividual Differences in In Vitro Human Intestinal Microbial Conversion of 3-Acetyl-DON and 15-Acetyl-DON.Toxins · 2022Article
- MicroRNA regulates the toxicological mechanism of four mycotoxins in vivo and in vitro.Journal of animal science and biotechnology · 2022Review
- Differential ER stress as a driver of cell fate following ricin toxin exposure.FASEB bioAdvances · 2022Article
- Mucosal ribosomal stress-induced PRDM1 promotes chemoresistance via stemness regulation.Communications biology · 2021Article
- Biomarkers of Deoxynivalenol Toxicity in Chickens with Special Emphasis on Metabolic and Welfare Parameters.Toxins · 2021Review
- The Potential Role of Protein Kinase R as a Regulator of Age-Related Neurodegeneration.Frontiers in aging neuroscience · 2021Review
- Cell fate determined by the activation balance between PKR and SPHK1.Cell death and differentiation · 2021Article
- News from Mars: Two-Tier Paradox, Intracellular PCR, Chimeric Junction Shift, Dark Matter mRNA and Other Remarkable Features of Mammalian RNA-Dependent mRNA Amplification. Implications for Alzheimer's Disease, RNA-Based Vaccines and mRNA Therapeutics.Annals of integrative molecular medicine · 2021Article
- Anticancer Activities and Mechanism of Action of Nagilactones, a Group of Terpenoid Lactones Isolated from Podocarpus Species.Natural products and bioprospecting · 2020Review
- Ribosomal stress-surveillance: three pathways is a magic number.Nucleic acids research · 2020Review
- Review
- Caveolar communication with xenobiotic-stalled ribosomes compromises gut barrier integrity.Communications biology · 2020Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Double-stranded RNA (dsRNA)-activated protein kinase (PKR) is a critical upstream mediator of the ribotoxic stress response (RSR) to the trichothecene deoxynivalenol (DON) and other translational inhibitors. Here, we employed HeLa cell lysates to: (1) characterize PKR's interactions with the ribosome and ribosomal RNA (rRNA); (2) demonstrate cell-free activation of ribosomal-associated PKR and (3) integrate these findings in a unified model for RSR. Robust PKR-dependent RSR was initially confirmed in intact cells. PKR basally associated with 40S, 60S, 80S and polysome fractions at molar ratios of 7, 2, 23 and 3, respectively. Treatment of ATP-containing HeLa lysates with DON or the ribotoxins anisomycin and ricin concentration-dependently elicited phosphorylation of PKR and its substrate eIF2α. These phosphorylations could be blocked by PKR inhibitors. rRNA immunoprecipitation (RNA-IP) of HeLa lysates with PKR-specific antibody and sequencing revealed that in the presence of DON or not, the kinase associated with numerous discrete sites on both the 18S and 28S rRNA molecules, a number of which contained double-stranded hairpins. These findings are consistent with a sentinel model whereby multiple PKR molecules basally associate with the ribosome positioning them to respond to ribotoxin-induced alterations in rRNA structure by dimerizing, autoactivating and, ultimately, evoking RSR.
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What OpenQuestion holds
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.