Cycloheximide can induce Bax/Bak dependent myeloid cell death independently of multiple BH3-only proteins
- Author(s)
- Goodall, KJ; Finch-Edmondson, ML; van Vuuren, J; Yeoh, GC; Gentle, IE; Vince, JE; Ekert, PG; Vaux, DL; Callus, BA;
- Details
- Publication Year 2016,Volume 11,Issue #11,Page e0164003
- Journal Title
- PLoS One
- Publication Type
- Journal Article
- 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.
- Publisher
- PLOS
- Research Division(s)
- Inflammation; Cell Signalling And Cell Death
- PubMed ID
- 27806040
- Publisher's Version
- https://doi.org/10.1371/journal.pone.0164003
- Open Access at Publisher's Site
http://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0164003- NHMRC Grants
- NHMRC/461221, NHMRC/1016701, NHMRC/384404,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2016-11-14 11:36:22
Last Modified: 2016-11-17 11:47:34