Evidence map›Paper›PMID 16966373›Full record

ArticleMolecular and cellular biology2006

Apoptosome-independent activation of the lysosomal cell death pathway by caspase-9.

Mads Gyrd-Hansen, Thomas Farkas, Nicole Fehrenbacher, Lone Bastholm, Maria Høyer-Hansen, Folmer Elling, David Wallach, Richard Flavell, Guido Kroemer, Jesper Nylandsted and 1 more

Erratum issuedOpen access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
3.9field-weighted citation impact, top 6% 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, 110 citations in OpenAlex.

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  16. Synergistic Antitumour Properties ofJournal of immunology research · 2017
    Article
  17. The role of lysosome in cell death regulation.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Review
  18. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 4 countries.

Mads Gyrd-HansenApoptosis Department and Centre for Genotoxic Stress, Institute for Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark.
Thomas Farkas
Nicole Fehrenbacher
Lone Bastholm
Maria Høyer-Hansen
Folmer Elling
David Wallach
Richard Flavell
Guido Kroemer
Jesper Nylandsted
Marja Jäättelä
Danish Cancer Society · DKUniversity of Copenhagen · DKHoward Hughes Medical Institute · USInstitut Gustave Roussy · FRWeizmann Institute of Science · IL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The apoptosome, a heptameric complex of Apaf-1, cytochrome c, and caspase-9, has been considered indispensable for the activation of caspase-9 during apoptosis. By using a large panel of genetically modified murine embryonic fibroblasts, we show here that, in response to tumor necrosis factor (TNF), caspase-8 cleaves and activates caspase-9 in an apoptosome-independent manner. Interestingly, caspase-8-cleaved caspase-9 induced lysosomal membrane permeabilization but failed to activate the effector caspases whereas apoptosome-dependent activation of caspase-9 could trigger both events. Consistent with the ability of TNF to activate the intrinsic apoptosis pathway and the caspase-9-dependent lysosomal cell death pathway in parallel, their individual inhibition conferred only a modest delay in TNF-induced cell death whereas simultaneous inhibition of both pathways was required to achieve protection comparable to that observed in caspase-9-deficient cells. Taken together, the findings indicate that caspase-9 plays a dual role in cell death signaling, as an activator of effector caspases and lysosomal membrane permeabilization.

Indexed as

AnimalsApoptosisApoptotic Protease-Activating Factor 1Caspase 8Caspase 9Cells, CulturedCycloheximideCytochromes cEnzyme ActivationFibroblastsLysosomesMiceMice, KnockoutMitochondriaProtein Synthesis InhibitorsTumor Necrosis Factor-alphaApoptotic Protease-Activating Factor 1Caspase 8Caspase 9CycloheximideCytochromes cProtein Synthesis InhibitorsTumor Necrosis Factor-alpha

Identifiers

PMID16966373
PMCPMC1636747
OpenAlexW2140865453

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.