Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies
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Apoptosis / physiology*
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Carrier Proteins / biosynthesis
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Cloning, Molecular
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Humans
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Macromolecular Substances
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Mammals
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Mice
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Molecular Sequence Data
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2*
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Saccharomyces cerevisiae
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Sequence Homology, Amino Acid
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Transfection
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bcl-Associated Death Protein
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bcl-X Protein
Substances
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Antibodies
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BAD protein, human
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BCL2L1 protein, human
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Bad protein, mouse
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Bcl2l1 protein, mouse
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Carrier Proteins
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Macromolecular Substances
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Recombinant Proteins
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bcl-Associated Death Protein
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bcl-X Protein