Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death.
To extend the mammalian cell death pathway, we screened for further Bcl-2 interacting proteins. Both yeast two-hybrid screening and lambda expression cloning identified a novel interacting protein, Bad, whose homology to Bcl-2 is limited to the BH1 and BH2 domains. Bad selectively dimerized with Bcl-xL as well as Bcl-2, but ... not with Bax, Bcl-xs, Mcl-1, A1, or itself. Bad binds more strongly to Bcl-xL than Bcl-2 in mammalian cells, and it reversed the death repressor activity of Bcl-xL, but not that of Bcl-2. When Bad dimerized with Bcl-xL, Bax was displaced and apoptosis was restored. When approximately half of Bax was heterodimerized, death was inhibited. The susceptibility of a cell to a death signal is determined by these competing dimerizations in which levels of Bad influence the effectiveness of Bcl-2 versus Bcl-xL in repressing death.
Mesh Terms:
Amino Acid Sequence, Animals, Antibodies, Apoptosis, Carrier Proteins, Cloning, Molecular, Humans, Macromolecular Substances, Mammals, Mice, Molecular Sequence Data, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Recombinant Proteins, Saccharomyces cerevisiae, Sequence Homology, Amino Acid, Transfection, bcl-Associated Death Protein, bcl-X Protein
Amino Acid Sequence, Animals, Antibodies, Apoptosis, Carrier Proteins, Cloning, Molecular, Humans, Macromolecular Substances, Mammals, Mice, Molecular Sequence Data, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Recombinant Proteins, Saccharomyces cerevisiae, Sequence Homology, Amino Acid, Transfection, bcl-Associated Death Protein, bcl-X Protein
Cell
Date: Jan. 27, 1995
PubMed ID: 7834748
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