A peptide sequence from Bax that converts Bcl-2 into an activator of apoptosis.
Bcl-2 and Bax are members of a family of cytoplasmic proteins that regulate apoptosis. The two proteins have highly similar amino acid sequences but are functionally opposed: Bcl-2 acts to inhibit apoptosis, whereas Bax counteracts this effect. The antagonism appears to depend upon dimerization between Bcl-2 and Bax, but its mechanism is otherwise unknown. Here we report that overexpressing Bax induces apoptosis in a mammalian fibroblast cell line, and we identify a novel, short "suicide domain" in Bax that is required for this effect. Inserting this domain in place of the corresponding, divergent sequence in Bcl-2 converts Bcl-2 from an inhibitor into an activator of cell death. These findings imply that a specific region in Bax confers an active propensity for apoptosis in mammalian cells and support the view that Bcl-2 may block death primarily by suppressing Bax activity.
Hunter
J J
JJ
Department of Pathology, University of California, San Francisco, 94143-0506, USA.
Parslow
T G
TG
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; C494827:Bax protein, mouse; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein