TITLE

c-Myc induces cytochrome c release in Rat1 fibroblasts by increasing outer mitochondrial membrane permeability in a Bid-dependent manner

AUTHOR(S)
Iaccarino, I; Hancock, D; Evan, G; Downward, J
PUB. DATE
May 2003
SOURCE
Cell Death & Differentiation;May2003, Vol. 10 Issue 5, p599
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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[SUBL]. 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.
ACCESSION #
9650019

 

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