ArticleInfection and immunity1999
Proteasome activity is required for anthrax lethal toxin to kill macrophages.
Article in Infection and immunity, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
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Who cites it
38 citing papers in PubMed, 118 citations in OpenAlex.
- Review
- Innate Sensors Trigger Regulated Cell Death to Combat Intracellular Infection.Annual review of immunology · 2022Review
- The NLRP1 and CARD8 inflammasomes.Immunological reviews · 2020Review
- The NLRP1 inflammasome: new mechanistic insights and unresolved mysteries.Current opinion in immunology · 2019Review
- The N-end rule ubiquitin ligase UBR2 mediates NLRP1B inflammasome activation by anthrax lethal toxin.The EMBO journal · 2019Article
- N-terminal degradation activates the NLRP1B inflammasome.Science (New York, N.Y.) · 2019Article
- Functional degradation: A mechanism of NLRP1 inflammasome activation by diverse pathogen enzymes.Science (New York, N.Y.) · 2019Article
- Inhibition of Dpp8/9 Activates the Nlrp1b Inflammasome.Cell chemical biology · 2018Article
- Anti-proliferative role of recombinant lethal toxin of Bacillus anthracis on primary mammary ductal carcinoma cells revealing its therapeutic potential.Oncotarget · 2017Article
- Proteolysis, synaptic plasticity and memory.Neurobiology of learning and memory · 2017Review
- Inhibitors of the Metalloproteinase Anthrax Lethal Factor.Current topics in medicinal chemistry · 2016Review
- Proteasome modulates positive and negative translational regulators in long-term synaptic plasticity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Local ubiquitin-proteasome-mediated proteolysis and long-term synaptic plasticity.Frontiers in molecular neuroscience · 2014Review
- Chemical genetics reveals a kinase-independent role for protein kinase R in pyroptosis.Nature chemical biology · 2013Article
- Activation of the Nlrp1b inflammasome by reduction of cytosolic ATP.Infection and immunity · 2013Article
- Article
- Salinosporamide natural products: Potent 20 S proteasome inhibitors as promising cancer chemotherapeutics.Angewandte Chemie (International ed. in English) · 2010Review
- Proteasome inhibitors prevent caspase-1-mediated disease in rodents challenged with anthrax lethal toxin.The American journal of pathology · 2010Article
- The ubiquitin-proteasome pathway and synaptic plasticity.Learning & memory (Cold Spring Harbor, N.Y.) · 2010Review
- The role of NF-kappaB and H3K27me3 demethylase, Jmjd3, on the anthrax lethal toxin tolerance of RAW 264.7 cells.PloS one · 2010Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Anthrax lethal toxin (LeTx), consisting of protective antigen (PA) and lethal factor (LF), rapidly kills primary mouse macrophages and macrophage-like cell lines such as RAW 264.7. LF is translocated by PA into the cytosol of target cells, where it acts as a metalloprotease to cleave mitogen-activated protein kinase kinase 1 (MEK1) and possibly other proteins. In this study, we show that proteasome inhibitors such as acetyl-Leu-Leu-norleucinal, MG132, and lactacystin efficiently block LeTx cytotoxicity, whereas other protease inhibitors do not. The inhibitor concentrations that block LF cytotoxicity are similar to those that inhibit the proteasome-dependent IkappaB-alpha degradation induced by lipopolysaccharide. The inhibitors did not interfere with the proteolytic cleavage of MEK1 in LeTx-treated cells, indicating that they do not directly block the proteolytic activity of LF. However, the proteasome inhibitors did prevent ATP depletion, an early effect of LeTx. No overall activation of the proteasome by LeTx was detected, as shown by the cleavage of fluorogenic substrates of the proteasome. All of these results suggest that the proteasome mediates a toxic process initiated by LF in the cell cytosol. This process probably involves degradation of unidentified molecules that are essential for macrophage homeostasis. Moreover, this proteasome-dependent process is an early step in LeTx intoxication, but it is downstream of the cleavage by LF of MEK1 or other putative substrates.
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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.