Journal
CELL DEATH AND DIFFERENTIATION
Volume 10, Issue 5, Pages 599-608Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.cdd.4401211
Keywords
c-Myc; apoptosis; mitochondria; cytochrome c; bid; Bax; BH3
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Ectopic expression of c-myc sensitises cells to a wide range of apoptotic stimuli by inducing the release of cytochrome c from the mitochondrial intermembrane space into the cytosol. To elucidate the molecular mechanisms of mitochondrial permeabilisation in response to c-Myc activation, we carried out a biochemical fractionation analysis of Rat1 fibroblasts expressing an inducible c-Myc protein. We find that cytoplasmic extracts from cells in which c-Myc has been activated contain a soluble factor capable of inducing cytochrome c release from isolated mouse liver mitochondria. This factor is present only under growth factor deprivation conditions and its activity is inhibited by addition of Bcl-X-L. The c-Myc-induced factor copurifies with full-length Bid, a BH3-only proapoptotic member of the Bcl-2 family, and antibodies raised against the BH3 domain of Bid inhibit c-Myc-induced cytochrome c releasing activity. These results are consistent with a model in which the activation of c-Myc regulates factors capable of enhancing the mitochondrial membrane destabilisation function of BH3-only proteins.
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