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• W2299192829 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." @default.
• W2299192829 created "2016-06-24" @default.
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• W2299192829 date "2016-02-02" @default.
• W2299192829 modified "2023-10-15" @default.
• W2299192829 title "Mito-priming as a method to engineer Bcl-2 addiction" @default.
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• W2299192829 doi "https://doi.org/10.1038/ncomms10538" @default.
• W2299192829 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4740867" @default.
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• W2299192829 hasPublicationYear "2016" @default.
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