c-Myc induces cytochrome c release in Rat1 fibroblasts by increasing outer mitochondrial membrane permeability in a Bid-dependent manner.
Cell Death Differ
; 10(5): 599-608, 2003 May.
Article
en En
| MEDLINE
| ID: mdl-12728258
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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tamoxifeno
/
Mitocondrias Hepáticas
/
Proteínas Portadoras
/
Permeabilidad de la Membrana Celular
/
Proteínas Proto-Oncogénicas c-myc
/
Citocromos c
/
Fibroblastos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Cell Death Differ
Año:
2003
Tipo del documento:
Article
Pais de publicación:
Reino Unido