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Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
Open accessAbstract
We show that the antiapoptotic proteins BCL-2, BCL-XL, MCL-1, BFL-1, and BCL-w each bear a unique pattern of interaction with a panel of peptides derived from BH3 domains of BH3-only proteins. Cellular dependence on an antiapoptotic protein for survival can be decoded based on the pattern of mitochondrial sensitivity to this peptide panel, a strategy that we call BH3 profiling. Dependence on antiapoptotic proteins correlates with sequestration of activator BH3-only proteins like BID or BIM by antiapoptotic proteins. Sensitivity to the cell-permeable BCL-2 antagonist ABT-737 is also related to priming of BCL-2 by activator BH3-only molecules. Our data allow us to distinguish a cellular state we call "primed for death," which can be determined by BH3 profiling and which correlates with dependence on antiapoptotic family members for survival.
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Metadata
- Authors
- Certo, M., Moore, V. D. G., Nishino, M., Wei, G., Korsmeyer, S., Armstrong, S. A., & Letai, A.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2006-05
- Volume
- 9
- Issue
- 5
- Pages
- 351-365
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2097007474
- Cited by
- 1,288
- References
- 5
- FWCI
- 28.98
- Type
- journal article
- Language
- en
- Open access
- bronze
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