Literature DB >> 16697956

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

Michael Certo1, Victoria Del Gaizo Moore, Mari Nishino, Guo Wei, Stanley Korsmeyer, Scott A Armstrong, Anthony Letai.   

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.

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Year:  2006        PMID: 16697956     DOI: 10.1016/j.ccr.2006.03.027

Source DB:  PubMed          Journal:  Cancer Cell        ISSN: 1535-6108            Impact factor:   31.743


  554 in total

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