Evidence map›Paper›PMID 27882936›Full record

ArticleNature communications2016

The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities.

Chu-Chiao Wu, Sunhee Lee, Srinivas Malladi, Miao-Der Chen, Nicholas J Mastrandrea, Zhiwen Zhang, Shawn B Bratton

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
4.7field-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

46 citing papers in PubMed, 82 citations in OpenAlex.

  1. Anoikis in cancer: molecular mechanisms, resistance, and therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026
    Review
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  9. CytochromeSaudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024
    Review
  10. Review
  11. Article
  12. Article
  13. Article
  14. Activation of caspase-9 on the apoptosome as studied by methyl-TROSY NMR.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. New Steroidal Selenides as Proapoptotic Factors.Molecules (Basel, Switzerland) · 2023
    Article
  16. Review
  17. Article
  18. Review
  19. Article
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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

7 authors at 3 institutions in 1 country.

Chu-Chiao WuDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.
Sunhee LeeDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.
Srinivas MalladiInstitute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
Miao-Der ChenDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.
Nicholas J MastrandreaDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.
Zhiwen ZhangBioengineering Department, Santa Clara University, Santa Clara, California 95053, USA.
Shawn B BrattonDepartment of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA.
The University of Texas MD Anderson Cancer Center · USThe University of Texas at Austin · USSanta Clara University · US

Funding

Heat shock-induced apoptosisR01CA129521 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BRATTON, SHAWN B · 2008 to 2012
$1.5M
Caspase-activating ComplexesR01GM096101 · NIGMS · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BRATTON, SHAWN B · 2011 to 2014
$1.2M
NCI NIH HHS R01 CA129521NIGMS NIH HHS R01 GM096101
6 · The paper itself

Abstract

According to dogma, initiator caspases are activated through proximity-induced homodimerization, but some studies infer that during apoptosis caspase-9 may instead form a holoenzyme with the Apaf-1 apoptosome. Using several biochemical approaches, including a novel site-specific crosslinking technique, we provide the first direct evidence that procaspase-9 homodimerizes within the apoptosome, markedly increasing its avidity for the complex and inducing selective intramolecular cleavage at Asp-315. Remarkably, however, procaspase-9 could also bind via its small subunit to the NOD domain in Apaf-1, resulting in the formation of a heterodimer that more efficiently activated procaspase-3. Following cleavage, the intersubunit linker (and associated conformational changes) in caspase-9-p35/p12 inhibited its ability to form homo- and heterodimers, but feedback cleavage by caspase-3 at Asp-330 removed the linker entirely and partially restored activity to caspase-9-p35/p10. Thus, the apoptosome mediates the formation of caspase-9 homo- and heterodimers, both of which are impacted by cleavage and contribute to its overall function.

Indexed as

ApoptosisAnimalsApoptosomesApoptotic Protease-Activating Factor 1Caspase 3Caspase 9DimerizationMicePhosphotransferasesProtein KinasesSf9 CellsSpodopteraTumor Suppressor ProteinsApaf1 protein, mouseApoptosomesApoptotic Protease-Activating Factor 1Casp3 protein, mouseCasp9 protein, mouseCaspase 3Caspase 9Cdk2ap1 protein, mouseCdk5r1 protein, mousePhosphotransferasesProtein KinasesTumor Suppressor Proteins

Identifiers

PMID27882936
PMCPMC5123071
OpenAlexW2556287713

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.