Evidence map›Paper›PMID 27806040›Full record

ArticlePloS one2016

Cycloheximide Can Induce Bax/Bak Dependent Myeloid Cell Death Independently of Multiple BH3-Only Proteins.

Katharine J Goodall, Megan L Finch-Edmondson, Joanne van Vuuren, George C Yeoh, Ian E Gentle, James E Vince, Paul G Ekert, David L Vaux, Bernard A Callus

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

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

5 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. 2-5A-Mediated decay (2-5AMD): from antiviral defense to control of host RNA.Critical reviews in biochemistry and molecular biology
    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

9 authors at 8 institutions in 2 countries.

Katharine J GoodallDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Megan L Finch-EdmondsonSchool of Chemistry and Biochemistry, University of Western Australia, Crawley, WA, Australia.
Joanne van VuurenHarry Perkins Institute of Medical Research, QEII Medical Centre, Nedlands and Centre for Medical Research, the University of Western Australia, Crawley, WA, Australia.
George C YeohSchool of Chemistry and Biochemistry, University of Western Australia, Crawley, WA, Australia.
Ian E GentleDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
James E VinceDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Paul G EkertDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
David L VauxDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
Bernard A CallusDepartment of Biochemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.
University of Western Australia · AUHarry Perkins Institute of Medical Research · AUInstitute of Medical Microbiology and Hygiene · DELa Trobe University · AUMurdoch Children's Research Institute · AUQueen Elizabeth II Medical Centre · AUUniversity of Melbourne · AUWalter and Eliza Hall Institute of Medical Research · AU

Funding

Worldwide Cancer Research 09-0084
6 · The paper itself

Abstract

Apoptosis mediated by Bax or Bak is usually thought to be triggered by BH3-only members of the Bcl-2 protein family. BH3-only proteins can directly bind to and activate Bax or Bak, or indirectly activate them by binding to anti-apoptotic Bcl-2 family members, thereby relieving their inhibition of Bax and Bak. Here we describe a third way of activation of Bax/Bak dependent apoptosis that does not require triggering by multiple BH3-only proteins. In factor dependent myeloid (FDM) cell lines, cycloheximide induced apoptosis by a Bax/Bak dependent mechanism, because Bax-/-Bak-/- lines were profoundly resistant, whereas FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Addition of cycloheximide led to the rapid loss of Mcl-1 but did not affect the expression of other Bcl-2 family proteins. In support of these findings, similar results were observed by treating FDM cells with the CDK inhibitor, roscovitine. Roscovitine reduced Mcl-1 abundance and caused Bax/Bak dependent cell death, yet FDM lines lacking one or more genes for BH3-only proteins remained highly sensitive. Therefore Bax/Bak dependent apoptosis can be regulated by the abundance of anti-apoptotic Bcl-2 family members such as Mcl-1, independently of several known BH3-only proteins.

Indexed as

AnimalsApoptosisApoptosis Regulatory Proteinsbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCell DeathCell LineCycloheximideDose-Response Relationship, DrugGene Knockout TechniquesHumansMiceMyeloid CellsProteasome Endopeptidase ComplexProtein Synthesis InhibitorsProto-Oncogene Proteins c-bcl-2Apoptosis Regulatory Proteinsbcl-2-Associated X Proteinbcl-2 Homologous Antagonist-Killer ProteinCycloheximideProteasome Endopeptidase ComplexProtein Synthesis InhibitorsProto-Oncogene Proteins c-bcl-2

Identifiers

PMID27806040
PMCPMC5091851
OpenAlexW2547162990

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.