Evidence map›Paper›PMID 20173201›Full record

ArticleMolecular & cellular proteomics : MCP2010

Inflammatory stimuli regulate caspase substrate profiles.

Nicholas J Agard, David Maltby, James A Wells

Open access · hybridAbstract read
In one paragraph

Article in Molecular & cellular proteomics : MCP, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

113 citing papers in PubMed, 217 citations in OpenAlex.

  1. Review
  2. Article
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  4. Review
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  6. Review
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  8. Review
  9. Article
  10. Review
  11. Inflammasomes primarily restrict cytosolicbioRxiv : the preprint server for biology · 2024
    Article
  12. Article
  13. Review
  14. Article
  15. Mechanistic insights from inflammasome structures.Nature reviews. Immunology · 2024
    Review
  16. The gasdermin family: emerging therapeutic targets in diseases.Signal transduction and targeted therapy · 2024
    Review
  17. Article
  18. Review
  19. Article
  20. Caspase-1 Responsive Nanoreporter forACS applied materials & interfaces · 2023
    Article

53 more citing papers are in PubMed but not listed here.

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

3 authors at 1 institution in 1 country.

Nicholas J AgardDepartment of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, USA.
David Maltby
James A Wells
University of California, San Francisco · US

Funding

YEAST THREONINE &SERINE KINASESP41RR001614 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ORTIZ DE MONTELLANO, PAUL R · 1985 to 2011
$24.1M
Global Analysis of Proteolysis in ApoptosisR01GM081051 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2007 to 2015
$2.8M
Site-specific Allosteric Inhibitors for Inflammatory CaspasesR01AI070292 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WELLS, JAMES A · 2007 to 2011
$1.9M
PURCHASE OF MICRO LC/NANO ESIQQTOF MASS SPECTROMETERS10RR015804 · NCRR · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI BURLINGAME, ALMA L · 2001 to 2001
$500k
Global Analysis of Proteolysis in the Innate Immune ResponseF32AI077177 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGARD, NICHOLAS J. · 2008 to 2010
$143k
NCRR NIH HHS P41 RR001614NCRR NIH HHS P41RR001614NCRR NIH HHS RR015804NCRR NIH HHS S10 RR015804NIAID NIH HHS F32 AI077177NIAID NIH HHS F32AI077177NIAID NIH HHS R01 AI070292NIGMS NIH HHS R01 GM081051
6 · The paper itself

Abstract

The inflammatory caspases, human caspases-1, -4, and -5, proteolytically modulate diverse physiological outcomes in response to proinflammatory signals. Surprisingly, only a few substrates are known for these enzymes, including other caspases and the interleukin-1 family of cytokines. To more comprehensively characterize inflammatory caspase substrates, we combined an enzymatic N-terminal enrichment method with mass spectrometry-based proteomics to identify newly cleaved proteins. Analysis of THP-1 monocytic cell lysates treated with recombinant purified caspases identified 82 putative caspase-1 substrates, three putative caspase-4 substrates, and no substrates for caspase-5. By contrast, inflammatory caspases activated in THP-1 cells by mimics of gout (monosodium urate), bacterial infection (lipopolysaccharide and ATP), or viral infection (poly(dA.dT)) were found to cleave only 27, 16, and 22 substrates, respectively. Quantitative stable isotope labeling with amino acids in cell culture (SILAC) comparison of these three inflammatory stimuli showed that they induced largely overlapping substrate profiles but different extents of proteolysis. Interestingly, only half of the cleavages found in response to proinflammatory stimuli were contained within our set of 82 in vitro cleavage sites. These data provide the most comprehensive set of caspase-1-cleaved products reported to date and indicate that caspases-4 and -5 have far fewer substrates. Comparisons between the in vitro and in vivo data highlight the importance of localization in regulating inflammatory caspase activity. Finally, our data suggest that inducers of inflammation may subtly alter caspase-1 substrate profiles.

Indexed as

Amino Acid SequenceApoptosisBiotinylationCaspasesCell ExtractsCell LineEnzyme ActivationHumansHydrophobic and Hydrophilic InteractionsInflammationIsotope LabelingMolecular Sequence DataPeptidesPeptide SynthasesProtein BiosynthesisProtein Processing, Post-TranslationalCaspasesCell ExtractsPeptidesPeptide SynthasessubtiligaseSubtilisins

Identifiers

PMID20173201
PMCPMC2871421
OpenAlexW2097084610

What OpenQuestion holds

Textmetadata
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.