BH3 domain of BAD is required for heterodimerization with BCL-XL and pro-apoptotic activity.

BAD interacts with anti-apoptotic molecules BCL-2 and BCL-XL and promotes apoptosis. BAD is phosphorylated on serine residues in response to a survival factor, interleukin-3. Phosphorylated BAD cannot bind to BCL-XL or BCL-2 at membrane sites and is found in the cytosol bound to 14-3-3. We report here that deletion mapping ...
and site-directed mutagenesis identified a BH3 domain within BAD that proved necessary for both its heterodimerization with BCL-XL and its death agonist activity. Substitution of the conserved Leu151 with Ala in the BH3 amphipathic alpha-helix abrogated both functions. The BAD Leu151 mutant was predominantly in the cytosol bound to 14-3-3. The BH3 domain of BCL-2 also proved important for BCL-2/BAD interaction. These results establish a critical role for a BH3 domain within BAD and provide evidence that BAD may function as a death ligand whose pro-apoptotic activity requires heterodimerization with BCL-XL.
Mesh Terms:
Amino Acid Sequence, Animals, Apoptosis, Carrier Proteins, Cells, Cultured, Dimerization, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Proto-Oncogene Proteins c-bcl-2, Sequence Deletion, Sequence Homology, Amino Acid, bcl-Associated Death Protein, bcl-X Protein
J. Biol. Chem.
Date: Sep. 26, 1997
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