Lopez, J. et al. (2016) Mito-priming as a method of engineered Bcl-2 addiction. Nature Communications, 7, 10538. (doi: 10.1038/ncomms10538) (PMID:26833356) (PMCID:PMC4740867)
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Abstract
Most apoptotic stimuli require mitochondrial outer membrane permeabilization (MOMP) in order to execute cell death. As such, MOMP is subject to tight control by Bcl-2 family proteins. We have developed a powerful new technique to investigate Bcl-2-mediated regulation of MOMP. This method, called mito-priming, uses co-expression of pro- and anti-apoptotic Bcl-2 proteins to engineer Bcl-2 addiction. On addition of Bcl-2 targeting BH3 mimetics, mito-primed cells undergo apoptosis in a rapid and synchronous manner. Using this method we have comprehensively surveyed the efficacy of BH3 mimetic compounds, identifying potent and specific MCL-1 inhibitors. Furthermore, by combining different pro- and anti-apoptotic Bcl-2 pairings together with CRISPR/Cas9-based genome editing, we find that tBID and PUMA can preferentially kill in a BAK-dependent manner. In summary, mito-priming represents a facile and robust means to trigger mitochondrial apoptosis.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Ichim, Dr Gabriel and Riley, Dr Joel and Rochegue, Mr Tony and Tait, Professor Stephen |
| Authors: | Lopez, J., Bessou, M., Riley, J. S., Giampazolias, E., Todt, F., Rochegüe, T., Oberst, A., Green, D. R., Edlich, F., Ichim, G., and Tait, S. W.G. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Nature Communications |
| Publisher: | Nature Publishing Group |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright © 2016 Lopez, J. et al |
| Publisher Policy: | Reproduced under a Creative Commons License |
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