Accession Number:

ADA383343

Title:

Molecular Interactions of Bc1-2 Family Members in Breast Cancer Cells

Descriptive Note:

Final rept. 1 Sep 1996-31 Aug 2000

Corporate Author:

MICHIGAN UNIV ANN ARBOR

Personal Author(s):

Report Date:

2000-08-01

Pagination or Media Count:

66.0

Abstract:

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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research
  • Atomic and Molecular Physics and Spectroscopy

Distribution Statement:

APPROVED FOR PUBLIC RELEASE