Evidence map›Paper›PMID 12067274›Full record

ArticleThe Biochemical journal2002

Inhibitor specificity of recombinant and endogenous caspase-9.

Ciara A Ryan, Henning R Stennicke, Victor E Nava, Jennifer B Burch, J Marie Hardwick, Guy S Salvesen

Open access · bronzeAbstract read
In one paragraph

Article in The Biochemical journal, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 22% 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

18 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Article
  3. Intrinsic-mediated caspase activation is essential for cardiomyocyte hypertrophy.Proceedings of the National Academy of Sciences of the United States of America · 2013
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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

6 authors at 2 institutions in 1 country.

Ciara A RyanProgram for Apoptosis and Cell Death Research, The Burnham Institute, 10901 North, Torrey Pines Road, La Jolla, CA 92037, USA.
Henning R Stennicke
Victor E Nava
Jennifer B Burch
J Marie Hardwick
Guy S Salvesen
Johns Hopkins University · USSanford Burnham Prebys Medical Discovery Institute · US

Funding

PROTEASES IN NEURONAL CELL DEATHR01NS037878 · NINDS · SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE · PI SALVESEN, GUY S. · 1998 to 2007
$2.5M
REGULATION OF VIRAL INFECTIONS BY CELLULAR GENESR01NS034175 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HARDWICK, J. MARIE · 1995 to 2009
$2.5M
INHIBITION OF PROTEASES BY IAPSR01AG015402 · NIA · BURNHAM INSTITUTE FOR MEDICAL RESEARCH · PI SALVESEN, GUY S · 1998 to 2005
$2.3M
NIA NIH HHS AG15402NINDS NIH HHS NS34175NINDS NIH HHS NS37878
6 · The paper itself

Abstract

Apoptosis triggered through the intrinsic pathway by radiation and anti-neoplastic drugs is initiated by the activation of caspase-9. To elucidate control mechanisms in this pathway we used a range of synthetic and natural reagents. The inhibitory potency of acetyl-Asp-Glu-Val-Asp-aldehyde ('Ac-DEVD-CHO'), benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone ('Z-VAD-FMK') and the endogenous caspase inhibitor X-chromosome-linked inhibitor of apoptosis protein ('XIAP') against recombinant caspase-9 were predictive of the efficacy of these compounds in a cell-free system. However, the viral proteins CrmA and p35, although potent inhibitors of recombinant caspase-9, had almost no ability to block caspase-9 in this system. These findings were also mirrored in cell expression studies. We hypothesize that the viral inhibitors CrmA and p35 are excluded from reacting productively with the natural form of active caspase-9 in vivo, making the potency of inhibitors highly context-dependent. This is supported by survival data from a mouse model of apoptosis driven by Sindbis virus expressing either p35 or a catalytic mutant of caspase-9. These results consolidate previous findings that CrmA is a potent inhibitor of caspase-9 in vitro, yet fails to block caspase-9-mediated cell death.

Indexed as

Caspase InhibitorsAmino Acid Chloromethyl KetonesApoptosisCaspase 9Cell LineCysteine Proteinase InhibitorsHumansKidneyKineticsOligopeptidesProteinsRecombinant ProteinsSubstrate SpecificityX ChromosomeX-Linked Inhibitor of Apoptosis ProteinZinc Fingersacetyl-aspartyl-glutamyl-valyl-aspartalAmino Acid Chloromethyl Ketonesbenzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketoneCASP9 protein, humanCasp9 protein, mouseCaspase 9Caspase InhibitorsCysteine Proteinase InhibitorsOligopeptidesProteinsRecombinant ProteinsXIAP protein, humanX-Linked Inhibitor of Apoptosis Protein

Identifiers

PMID12067274
PMCPMC1222808
OpenAlexW2031701445

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.