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BID: a novel BH3 domain-only death agonist.

Genes & development | Nov 15, 1996

http://www.ncbi.nlm.nih.gov/pubmed/8918887

The BCL-2 family of proteins consists of both antagonists (e.g., BCL-2) and agonists (e.g., BAX) that regulate apoptosis and compete through dimerization. The BH1 and BH2 domains of BCL-2 are required to heterodimerize with BAX and to repress cell death; conversely, the BH3 domain of BAX is required to heterodimerize with BCL-2 and to promote cell death. To extend this pathway, we used interactive cloning to identify Bid, which encodes a novel death agonist that heterodimerizes with either agonists (BAX) or antagonists (BCL-2). BID possesses only the BH3 domain, lacks a carboxy-terminal signal-anchor segment, and is found in both cytosolic and membrane locations. BID counters the protective effect of BCL-2. Moreover, expression of BID, without another death stimulus, induces ICE-like proteases and apoptosis. Mutagenesis revealed that an intact BH3 domain of BID was required to bind the BH1 domain of either BCL-2 or BAX. A BH3 mutant of BID that still heterodimerized with BCL-2 failed to promote apoptosis, dissociating these activities. In contrast, the only BID BH3 mutant that retained death promoting activity interacted with BAX, but not BCL-2. This BH3-only molecule supports BH3 as a death domain and favors a model in which BID represents a death ligand for the membrane-bound receptor BAX.

Pubmed ID: 8918887 RIS Download

Mesh terms: Amino Acid Chloromethyl Ketones | Amino Acid Sequence | Animals | Apoptosis | BH3 Interacting Domain Death Agonist Protein | Carrier Proteins | Caspase 1 | Cloning, Molecular | Cysteine Endopeptidases | Cysteine Proteinase Inhibitors | Enzyme Induction | Humans | Mice | Models, Biological | Molecular Sequence Data | Protein Binding | Protein Conformation | Proto-Oncogene Proteins | Proto-Oncogene Proteins c-bcl-2 | Recombinant Proteins | Sequence Homology, Amino Acid | Signal Transduction | Species Specificity | bcl-2-Associated X Protein

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Associated grants

  • Agency: NCI NIH HHS, Id: CA50239

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