A PEPTIDE SEQUENCE FROM BAX THAT CONVERTS BCL-2 INTO AN ACTIVATOR OF APOPTOSIS

Bcl-2 and Bar are members of a family of cytoplasmic proteins that reg ulate apoptosis. The two proteins have highly similar amino acid seque nces but are functionally opposed: Bcl-2 acts to inhibit apoptosis, wh ereas Bar counteracts this effect. The antagonism appears to depend up on dimerization between Bcl-2 and Bar, but its mechanism is otherwise unknown. Here we report that overexpressing Bar induces apoptosis in a mammalian fibroblast cell line, and we identify a novel, short ''suic ide domain'' in Bar that is required for this effect, Inserting this d omain in place of the corresponding, divergent sequence in Bcl-2 conve rts Bcl-2 from an inhibitor into an activator of cell death. These fin dings imply that a specific region in Bar confers an active propensity for apoptosis in mammalian cells and support the view that Bcl-2 may block death primarily by suppressing Bar activity.