Evidence map›Paper›PMID 23110696›Full record

ArticleThe Biochemical journal2013

The CARD plays a critical role in ASC foci formation and inflammasome signalling.

Martina Proell, Motti Gerlic, Peter D Mace, John C Reed, Stefan J Riedl

Abstract read
In one paragraph

Article in The Biochemical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. An overview of human inflammasomes: Activation and regulation.Journal of immunology (Baltimore, Md. : 1950) · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. The Evolution of NLR Inflammasome and Its Mediated Pyroptosis in Metazoa.International journal of molecular sciences · 2024
    Article
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. The NLRP3 inflammasome in viral infection (Review).Molecular medicine reports · 2023
    Review
  19. Article
  20. Review

32 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

5 authors at 1 institution in 1 country.

Martina ProellPrograms in Cell Death and Inflammation Research, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Rd, La Jolla, CA 92037, USA.
Motti Gerlic
Peter D Mace
John C Reed
Stefan J Riedl
Sanford Burnham Prebys Medical Discovery Institute · US

Funding

Project 4: A Developmental Perspective to Nitrosative/Oxidative SusceptibilityP01ES016738 · NIEHS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RIEDL, STEFAN J · 2008 to 2012
$8.5M
PAAD-Family Proteins and Host Defense MechanismsR01AI056324 · NIAID · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI REED, JOHN C · 2003 to 2012
$4.5M
The Mechanism of DISC FormationR01AA017238 · NIAAA · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI RIEDL, STEFAN J · 2008 to 2012
$2.1M
NIAAA NIH HHS R01 AA017238NIAAA NIH HHS R01AA017238NIAID NIH HHS AI-56324NIAID NIH HHS R01 AI056324NIEHS NIH HHS P01ES01673NIEHS NIH HHS P01 ES016738
6 · The paper itself

Abstract

The ASC (apoptosis speck-like protein) is a key component of multimeric protein complexes that mediate inflammation and host defence. Comprising a PYD (Pyrin) domain and a CARD (caspase activation and recruitment domain), ASC functions downstream of NLRs (nucleotide-binding domain, leucine-rich repeat-containing receptors) and AIM2 (absent in melanoma 2) through the formation of supramolecular structures termed inflammasomes. However, the mechanism underlying ASC signalling and its dependency on oligomeric arrangements in inflammasome formation remain poorly understood. When expressed in cells, ASC forms discrete foci (called 'specks') typically with one speck per cell. We employed a BiFC (bimolecular fluorescence complementation) system to investigate and visualize ASC foci formation in living cells. We demonstrated that the CARD of ASC plays a central role in ASC inflammasome assembly, representing the minimal unit capable of forming foci in conjunction with the caspase 1 CARD. Mutational studies point to multiple surfaces on the ASC CARD and two predominant areas on the caspase 1 CARD mediating the formation of ASC/caspase 1 foci. The lack of foci formation for ASC CARD mutants correlates with a loss of IL-1β (interleukin 1β) processing in response to NLRP (NLR family, PYD domain-containing) 3 or AIM2 agonists in RAW264.7 cell reconstitution assays. Analogously, we show that productive formation of the Salmonella typhimurium-induced NLRC4 (NLR family CARD domain-containing protein 4) inflammasome is dependent on ASC-CARD-mediated platform formation. Thus the results of the present study depict a central role of CARDs in the formation of ASC signalling platforms and provide an important tool for investigation of CARD-dependent networks.

Indexed as

AnimalsCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cell LineCytoskeletal ProteinsDNA-Binding ProteinsHEK293 CellsHeLa CellsHumansImmunity, InnateInflammasomesInterleukin-1betaMiceModels, MolecularAIM2 protein, humanCalcium-Binding ProteinsCARD Signaling Adaptor ProteinsCarrier ProteinsCaspase 1Cytoskeletal ProteinsDNA-Binding ProteinsInflammasomesInterleukin-1betaMultiprotein ComplexesMutant ProteinsNLRC4 protein, humanNLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNuclear ProteinsPYCARD protein, human

Identifiers

PMID23110696
PMCPMC3966062
OpenAlexW2089250915

What OpenQuestion holds

Textmetadata
LicenceTDM
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.