Evidence map›Paper›PMID 21157428›Full record

ArticleThe EMBO journal2011

Caspase-8 and caspase-7 sequentially mediate proteolytic activation of acid sphingomyelinase in TNF-R1 receptosomes.

Bärbel Edelmann, Uwe Bertsch, Vladimir Tchikov, Supandi Winoto-Morbach, Cristiana Perrotta, Marten Jakob, Sabine Adam-Klages, Dieter Kabelitz, Stefan Schütze

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

44 citing papers in PubMed, 102 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Ceramide in cerebrovascular diseases.Frontiers in cellular neuroscience · 2023
    Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Molecular Biology ofToxins · 2020
    Review
  15. Article
  16. The anticonvulsive PhenhydanCell death and differentiation · 2019
    Article
  17. Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019
    Article
  18. Review
  19. Review
  20. Article
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

9 authors at 2 institutions in 2 countries.

Bärbel EdelmannInstitute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Uwe Bertsch
Vladimir Tchikov
Supandi Winoto-Morbach
Cristiana Perrotta
Marten Jakob
Sabine Adam-Klages
Dieter Kabelitz
Stefan Schütze
Kiel University · DELuigi Sacco Hospital · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We previously demonstrated that tumour necrosis factor (TNF)-induced ceramide production by endosomal acid sphingomyelinase (A-SMase) couples to apoptosis signalling via activation of cathepsin D and cleavage of Bid, resulting in caspase-9 and caspase-3 activation. The mechanism of TNF-mediated A-SMase activation within the endolysosomal compartment is poorly defined. Here, we show that TNF-induced A-SMase activation depends on functional caspase-8 and caspase-7 expression. The active forms of all three enzymes, caspase-8, caspase-7 and A-SMase, but not caspase-3, colocalize in internalized TNF receptosomes. While caspase-8 and caspase-3 are unable to induce activation of purified pro-A-SMase, we found that caspase-7 mediates A-SMase activation by direct interaction resulting in proteolytic cleavage of the 72-kDa pro-A-SMase zymogen at the non-canonical cleavage site after aspartate 253, generating an active 57 kDa A-SMase molecule. Caspase-7 down modulation revealed the functional link between caspase-7 and A-SMase, confirming proteolytic cleavage as one further mode of A-SMase activation. Our data suggest a signalling cascade within TNF receptosomes involving sequential activation of caspase-8 and caspase-7 for induction of A-SMase activation by proteolytic cleavage of pro-A-SMase.

Indexed as

AnimalsApoptosisBlotting, WesternCaspase 7Caspase 8Cell LineCeramidesChromatography, Thin LayerCloning, MolecularEndosomesEnzyme ActivationFlow CytometryGene Knockdown TechniquesHumansJurkat CellsMiceacid sphingomyelinase-1Caspase 7Caspase 8CeramidesSphingomyelin PhosphodiesteraseTumor Necrosis Factor-alpha

Identifiers

PMID21157428
PMCPMC3025468
OpenAlexW1950343975

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.