Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members - PubMed (original) (raw)
Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
Michael Certo et al. Cancer Cell. 2006 May.
Free article
Abstract
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.
Comment in
- At the gates of death.
Green DR. Green DR. Cancer Cell. 2006 May;9(5):328-30. doi: 10.1016/j.ccr.2006.05.004. Cancer Cell. 2006. PMID: 16697952
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