Evidence map›Paper›PMID 25248749›Full record

ArticleThe Journal of biological chemistry2014

Auxin-induced rapid degradation of inhibitor of caspase-activated DNase (ICAD) induces apoptotic DNA fragmentation, caspase activation, and cell death: a cell suicide module.

Kumiko Samejima, Hiromi Ogawa, Alexander V Ageichik, Kevin L Peterson, Scott H Kaufmann, Masato T Kanemaki, William C Earnshaw

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.3field-weighted citation impact, top 21% 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

16 citing papers in PubMed, 32 citations in OpenAlex.

  1. Knockdown of caspase-activated DNase and B-cell lymphoma 2 inhibits cell proliferation and drug resistance in TP53-mutant multiple myeloma.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
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  6. Regulated cell death in cisplatin-induced AKI: relevance ofAmerican journal of physiology. Renal physiology · 2021
    Article
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  15. Engineered cellular gene-replacement platform for selective and inducible proteolytic profiling.Proceedings of the National Academy of Sciences of the United States of America · 2015
    Article
  16. Review
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 4 institutions in 3 countries.

Kumiko SamejimaFrom the Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom, kumiko.samejima@ed.ac.uk.
Hiromi OgawaFrom the Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom.
Alexander V AgeichikFrom the Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom.
Kevin L Petersonthe Mayo Clinic, Rochester, Minnesota 55905.
Scott H Kaufmannthe Mayo Clinic, Rochester, Minnesota 55905.
Masato T Kanemakithe Centre for Frontier Research, National Institute of Genetics, ROIS, and Department of Genetics, SOKENDAI, Yata 1111, Mishima, Shizuoka 411-8540, Japan, and the Japan Science and Technology Agency (JST), PREST, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
William C EarnshawFrom the Wellcome Trust Centre for Cell Biology, University of Edinburgh, King's Buildings, Max Born Crescent, Edinburgh EH9 3BF, Scotland, United Kingdom, bill.earnshaw@ed.ac.uk.
University of Edinburgh · GBMayo Clinic · USJapan Science and Technology Agency · JPWellcome Centre for Cell Biology · GB

Funding

Anticancer drug-induced BH3-only protein.Bak interactionsR01CA166741 · NCI · MAYO CLINIC ROCHESTER · PI KAUFMANN, SCOTT H · 2012 to 2016
$1.6M
NCI NIH HHS R01 CA166741Wellcome Trust 073915Wellcome Trust 077707Wellcome Trust 092076
6 · The paper itself

Abstract

Caspase-activated DNase (CAD) is a major apoptotic nuclease, responsible for DNA fragmentation and chromatin condensation during apoptosis. CAD is normally activated in apoptosis as a result of caspase cleavage of its inhibitory chaperone ICAD. Other aspects of CAD regulation are poorly understood. In particular, it has been unclear whether direct CAD activation in non-apoptotic living cells can trigger cell death. Taking advantage of the auxin-inducible degron (AID) system, we have developed a suicide system with which ICAD is rapidly degraded in living cells in response to the plant hormone auxin. Our studies demonstrate that rapid ICAD depletion is sufficient to activate CAD and induce cell death in DT40 and yeast cells. In the vertebrate cells, ectopic CAD activation triggered caspase activation and subsequent hallmarks of caspase-dependent apoptotic changes, including phosphatidylserine exposure and nuclear fragmentation. These observations not only suggest that CAD activation drives apoptosis through a positive feedback loop, but also identify a unique suicide system that can be used for controlling gene-modified organisms.

Indexed as

Gene Expression Regulation, EnzymologicAnimalsAnnexin A5ApoptosisApoptosis Regulatory ProteinsCaspasesCell DeathCell Line, TumorCell NucleusChickensDeoxyribonucleasesDNA FragmentationEnzyme ActivationFluorescent Antibody Technique, IndirectGene Knockout TechniquesIndoleacetic AcidsAnnexin A5Apoptosis Regulatory Proteinscaspase-activated DNase inhibitorCaspasesDeoxyribonucleasesIndoleacetic AcidsPhosphatidylserinesAnnexin VApoptosisAuxinCaspaseCaspase-activated DNase (CAD)Cell DeathDNA FragmentationInhibitor of Caspase-activated DNase (ICAD)TUNEL AssayYeast

Identifiers

PMID25248749
PMCPMC4223357
OpenAlexW1981944678

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.