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

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.

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Document Details

Document Type
Technical Report
Publication Date
Aug 01, 2000
Accession Number
ADA383343

Entities

People

  • Gabriel Nunez

Organizations

  • University of Michigan

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Apoptosis
  • Biomedical Research
  • Blood
  • Cell Line
  • Cell Physiological Processes
  • Cells
  • Chemistry
  • Confocal Microscopy
  • Crystal Structure
  • Fungi
  • Genetic Structures
  • Intracellular Membranes
  • Molecular Dynamics
  • Programmed Cell Death
  • Proteins
  • Tumor Cell Line

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Biology and Genetics

Technology Areas

  • Biotechnology