[HTML][HTML] Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members
M Certo, VDG Moore, M Nishino, G Wei, S Korsmeyer… - Cancer cell, 2006 - cell.com
M Certo, VDG Moore, M Nishino, G Wei, S Korsmeyer, SA Armstrong, A Letai
Cancer cell, 2006•cell.comWe 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 …
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 …
Summary
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.
cell.com