BID: A novel BH3 domain-only death agonist

Kun Wang, Xiao Ming Yin, Debra T. Chao, Curt L. Milliman, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

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Abstract

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 identity 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.

Original languageEnglish (US)
Pages (from-to)2859-2869
Number of pages11
JournalGenes and Development
Volume10
Issue number22
DOIs
StatePublished - Jan 1 1996

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Keywords

  • Apoptosis
  • BCL-2 family
  • BH3 domain
  • BID
  • cysteine protease

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Cite this

Wang, K., Yin, X. M., Chao, D. T., Milliman, C. L., & Korsmeyer, S. J. (1996). BID: A novel BH3 domain-only death agonist. Genes and Development, 10(22), 2859-2869. https://doi.org/10.1101/gad.10.22.2859