Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0164003
Title: Cycloheximide can induce bax/bak dependent myeloid cell death independently of multiple BH3-only proteins
Authors: Goodall K.J.
Finch-Edmondson M.L. 
Van Vuuren J.
Yeoh G.C.
Gentle I.E.
Vince J.E.
Ekert P.G.
Vaux D.L.
Callus B.A.
Keywords: BH3 protein
complementary DNA
cycloheximide
protein Bak
protein Bax
protein mcl 1
roscovitine
apoptosis regulatory protein
cycloheximide
proteasome
protein Bak
protein Bax
protein bcl 2
protein synthesis inhibitor
animal cell
animal cell culture
apoptosis
Article
bone marrow cell
cell viability
controlled study
cytolysis
immunoblotting
mouse
nonhuman
plasmid
protein depletion
protein expression
animal
apoptosis
bone marrow cell
cell death
cell line
dose response
drug effects
gene inactivation
genetics
human
metabolism
Animals
Apoptosis
Apoptosis Regulatory Proteins
bcl-2 Homologous Antagonist-Killer Protein
bcl-2-Associated X Protein
Cell Death
Cell Line
Cycloheximide
Dose-Response Relationship, Drug
Gene Knockout Techniques
Humans
Mice
Myeloid Cells
Proteasome Endopeptidase Complex
Protein Synthesis Inhibitors
Proto-Oncogene Proteins c-bcl-2
Issue Date: 2016
Publisher: Public Library of Science
Citation: Goodall K.J., Finch-Edmondson M.L., Van Vuuren J., Yeoh G.C., Gentle I.E., Vince J.E., Ekert P.G., Vaux D.L., Callus B.A. (2016). Cycloheximide can induce bax/bak dependent myeloid cell death independently of multiple BH3-only proteins. PLoS ONE 11 (11) : e0164003. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0164003
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. © 2016 Goodall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/165735
ISSN: 19326203
DOI: 10.1371/journal.pone.0164003
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