JCB logo
CrossRef
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published 2 September 2003. doi:10.1083/jcb.200302144
This Article
Right arrow Full Text
Right arrow PDF (Full Text)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Wilson-Annan, J.
Right arrow Articles by Huang, D. C.S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wilson-Annan, J.
Right arrow Articles by Huang, D. C.S.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0021-9525/2003/9/877 $5.00
The Journal of Cell Biology, Volume 162, Number 5, 877-888

Article

 Proapoptotic BH3-only proteins trigger membrane integration of prosurvival Bcl-w and neutralize its activity

Julie Wilson-Annan1, Lorraine A. O'Reilly1, Simon A. Crawford2, George Hausmann1, Jennifer G. Beaumont1, Loes P. Parma1, Lin Chen1, Martin Lackmann4, Trevor Lithgow3, Mark G. Hinds1, Catherine L. Day5, Jerry M. Adams1 and David C.S. Huang1

1 Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia
2 School of Botany, University of Melbourne, Victoria 3050, Australia
3 School of Biochemistry, University of Melbourne, Victoria 3050, Australia
4 Ludwig Institute of Cancer Research, Victoria 3050, Australia
5 Department of Biochemistry, University of Otago, Dunedin 9001, New Zealand

Address correspondence to David Huang, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Victoria 3050, Australia. Tel.: 61-3-9345-2649. Fax: 61-3-9347-0852. email: huang_d{at}wehi.edu.au

Prosurvival Bcl-2–like proteins, like Bcl-w, are thought to function on organelles such as the mitochondrion and to be targeted to them by their hydrophobic COOH-terminal domain. We unexpectedly found, however, that the membrane association of Bcl-w was enhanced during apoptosis. In healthy cells, Bcl-w was loosely attached to the mitochondrial membrane, but it was converted into an integral membrane protein by cytotoxic signals that induce binding of BH3-only proteins, such as Bim, or by the addition of BH3 peptides to lysates. As the structure of Bcl-w has revealed that its COOH-terminal domain occupies the hydrophobic groove where BH3 ligands bind, displacement of that domain by a BH3 ligand would displace the hydrophobic COOH-terminal residues, allowing their insertion into the membrane. To determine whether BH3 ligation is sufficient to induce the enhanced membrane affinity, or to render Bcl-w proapoptotic, we mimicked their complex by tethering the Bim BH3 domain to the NH2 terminus of Bcl-w. The chimera indeed bound avidly to membranes, in a fashion requiring the COOH-terminal domain, but neither promoted nor inhibited apoptosis. These results suggest that ligation of a proapoptotic BH3-only protein alters the conformation of Bcl-w, enhances membrane association, and neutralizes its survival function.

Key Words: Bcl-2; BH3; apoptosis; mitochondria; targeting

Abbreviations used in this paper: BH, Bcl-2 homology; PI, propidium iodide.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?

Related Article

Bcl-w buries its tail, lets cell die
Alan W. Dove
J. Cell Biol. 2003 162: 749. [Full Text] [PDF]



This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents