Accession Number:

ADB281660

Title:

Characterization of Bc1-2, Bc1-xL, and Bax Pore Formation and Their Role in Apoptosis Regulation

Descriptive Note:

Annual rept. 2 Jul 1998-31 Dec 2001

Corporate Author:

BURNHAM INST LA JOLLA CA

Report Date:

2002-01-01

Pagination or Media Count:

33.0

Abstract:

Bcl-2-family proteins are central regulators of apoptosis and their expression often becomes deregulated in breast cancers. The biochemical mechanisms by which Bcl-2 family proteins control cell life and death decisions are unknown. Recent evidence that certain Bcl-2 family proteins bear structural similarity to the pore-forming domains of bacterial toxin proteins suggest a function for these apoptosis regulators as ion-channels. Using eletrophysiological techniques, we demonstrated that the cytoprotective protein Bcl-2 and the cell death proteins Bax and Bid possess intrinsic ion-channel activity. A variety of structure-function studies demonstrated that channel formation by the Bcl-2 family proteins is important for some but not all of their bioactivities. This finding suggests novel ways to screen for drug inhibitors of Bcl-2, so that tumor cell resistance to cell death can be overcome and sensitivity to anticancer drugs restored

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE