Characterization of Bc1-2, Bc1-xL, and Bax Pore Formation and Their Role in Apoptosis Regulation
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
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2002
- Accession Number
- ADB281660
Entities
People
- Frank Stenner-liewen
- John C. Reed
- Sharon L. Schendel
Organizations
- Sanford Burnham Prebys Medical Discovery Institute