Bcl-w buries its tail, lets cell die

杨柳

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.
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8 w' o) C0 c8 c+ h& [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releases the COOH terminus, which then inserts into a membrane and neutralizes the pro-survival activity of Bcl-w. Unpublished data support a similar type of regulation for the pro-apoptotic protein Bcl-xL.(Bcl-w in dying cells buries its tail, pe)