Evidence map›Paper›PMID 17079734›Full record

ArticleMolecular biology of the cell2007

Loss of caspase-9 reveals its essential role for caspase-2 activation and mitochondrial membrane depolarization.

Ajoy K Samraj, Dennis Sohn, Klaus Schulze-Osthoff, Ingo Schmitz

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
–field-weighted citation impact
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

38 citing papers in PubMed.

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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

4 authors.

Ajoy K SamrajInstitute of Molecular Medicine, University of Düsseldorf, Düsseldorf D-40225, Germany.
Dennis Sohn
Klaus Schulze-Osthoff
Ingo Schmitz

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Caspase-9 plays an important role in apoptosis induced by genotoxic stress. Irradiation and anticancer drugs trigger mitochondrial outer membrane permeabilization, resulting in cytochrome c release and caspase-9 activation. Two highly contentious issues, however, remain: It is unclear whether the loss of the mitochondrial membrane potential DeltaPsi(M) contributes to cytochrome c release and whether caspases are involved. Moreover, an unresolved question is whether caspase-2 functions as an initiator in genotoxic stress-induced apoptosis. In the present study, we have identified a mutant Jurkat T-cell line that is deficient in caspase-9 and resistant to apoptosis. Anticancer drugs, however, could activate proapoptotic Bcl-2 proteins and cytochrome c release, similarly as in caspase-9-proficient cells. Interestingly, despite these alterations, the cells retained DeltaPsi(M). Furthermore, processing and enzyme activity of caspase-2 were not observed in the absence of caspase-9. Reconstitution of caspase-9 expression restored not only apoptosis but also the loss of DeltaPsi(M) and caspase-2 activity. Thus, we provide genetic evidence that caspase-9 is indispensable for drug-induced apoptosis in cancer cells. Moreover, loss of DeltaPsi(M) can be functionally separated from cytochrome c release. Caspase-9 is not only required for DeltaPsi(M) loss but also for caspase-2 activation, suggesting that these two events are downstream of the apoptosome.

Indexed as

Antineoplastic AgentsApoptosisbcl-2 Homologous Antagonist-Killer ProteinCaspase 2Caspase 9ChromatinCytochromes cDrug Resistance, NeoplasmEnzyme ActivationHumansInhibitor of Apoptosis ProteinsJurkat CellsMembrane Potential, MitochondrialMitochondrial MembranesMutagensStaurosporineAntineoplastic Agentsbcl-2 Homologous Antagonist-Killer ProteinCaspase 2Caspase 9ChromatinCytochromes cInhibitor of Apoptosis ProteinsMutagensStaurosporine

Identifiers

PMID17079734
PMCPMC1751323

What OpenQuestion holds

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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.