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© The Rockefeller University Press, 0021-9525/2003/9/749-a $5.00
The Journal of Cell Biology, Volume 162, Number 5, 749-a-749

Bcl-w buries its tail, lets cell die

Bcl-w in dying cells buries its tail, perhaps releasing a death effector.

Cells contemplate suicide by monitoring the opposing signals of pro-apoptotic and pro-survival members of the Bcl-2 protein family, but how are the pro-survival signals turned off when a cell initiates apoptosis? On page 877, Wilson-Annan et al. report that one pro-apoptotic signal causes Bcl-w, a pro-survival Bcl-2 protein, to stick itself into a membrane and become inert.Bcl-2 is an integral membrane protein, so it has long been assumed that its close relatives are also membrane integrated. However, the authors found that in healthy cells Bcl-w only associates loosely with membranes. Inducing apoptosis, however, causes Bcl-w to integrate into the mitochondrial membrane, an effect that is mimicked in cell lysates treated with a peptide from a BH3-only pro-apoptotic protein. Chimeric proteins with a BH3 domain attached to the NH₂ terminus of Bcl-w also integrate into membranes. Membrane-bound Bcl-w does not become pro-apoptotic, but it loses its pro-survival activity.

These results, and the recently solved structure of Bcl-w, suggest that Bcl-w normally keeps its hydrophobic COOH terminus folded into a groove on its surface. Binding to a BH3-only protein releases the COOH terminus, which then inserts into a membrane and neutralizes the pro-survival activity of Bcl-w. Unpublished data support a similar type of regulation for the pro-apoptotic protein Bcl-xL.

Alan W. Dove

alanwdove{at}earthlink.net

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

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J. Cell Biol. 2003 162: 877-888. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 845K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?