Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members.

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.
Mesh Terms:
Amino Acid Sequence, Animals, Apoptosis, Apoptosis Regulatory Proteins, BH3 Interacting Domain Death Agonist Protein, Biphenyl Compounds, Cell Line, Tumor, Enzyme Activators, Intracellular Membranes, Leukemia, Membrane Proteins, Mice, Mitochondria, Liver, Mitochondrial Membranes, Molecular Sequence Data, Nitrophenols, Peptide Fragments, Piperazines, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Signal Transduction, Sulfonamides
Cancer Cell
Date: May. 01, 2006
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