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BID: a novel BH3 domain-only death agonist.

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


  • Wang K
  • Yin XM
  • Chao DT
  • Milliman CL
  • Korsmeyer SJ


Genes & development

Publication Data

November 15, 1996

Associated Grants

  • Agency: NCI NIH HHS, Id: CA50239

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