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 Cheng Yeoh, Ian E Gentle, James E Vince, Paul G Ekert, David L. Vaux, Bernard A Callus

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3 Citations (Scopus)

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.

Original languageEnglish
Article numbere0164003
Number of pages18
JournalPLoS ONE
Volume11
Issue number11
DOIs
Publication statusPublished - 2 Nov 2016
Externally publishedYes

Cite this

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]. https://doi.org/10.1371/journal.pone.0164003