Molecular Interactions of Bc1-2 Family Members in Breast Cancer Cells
Final rept. 1 Sep 1996-31 Aug 2000
MICHIGAN UNIV ANN ARBOR
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A major genetic event that occurs in the pathogenesis of breast carcinoma involves alterations in the Bcl-2 survival pathway. We have performed studies to determine the mechanism involved in Bcl-xS-mediated apoptosis and to characterize cellular proteins that interact with Bcl-xS using biochemical and genetic approaches. The analysis showed that Bcl-xS requires its BH3 and C-terminal mitochondrial anchoring domains for killing. Bcl-XS-induced killing is, at least in part, mediated through an Apaf-l-caspase-9 pathway. Bcl-xS associates with Bcl-xL via its BH3 domain and with Apaf-l possibly through Bcl-xL. We have cloned and characterized several Apaf- 1 cDNAs and showed that a novel Apaf- 1 isoform activates procaspase-9 in a cytochrome c and dATP-dependent manner.
- Anatomy and Physiology
- Medicine and Medical Research
- Atomic and Molecular Physics and Spectroscopy