First Author | Certo M | Year | 2006 |
Journal | Cancer Cell | Volume | 9 |
Issue | 5 | Pages | 351-65 |
PubMed ID | 16697956 | Mgi Jnum | J:116441 |
Mgi Id | MGI:3694305 | Doi | 10.1016/j.ccr.2006.03.027 |
Citation | Certo M, et al. (2006) Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell 9(5):351-65 |
abstractText | 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. |