Bim: a novel member of the Bcl-2 family that promotes apoptosis

EMBO J. 1998 Jan 15;17(2):384-95. doi: 10.1093/emboj/17.2.384.


Certain members of the Bcl-2 family inhibit apoptosis while others facilitate this physiological process of cell death. An expression screen for proteins that bind to Bcl-2 yielded a small novel protein, denoted Bim, whose only similarity to any known protein is the short (nine amino acid) BH3 motif shared by most Bcl-2 homologues. Bim provokes apoptosis, and the BH3 region is required for Bcl-2 binding and for most of its cytotoxicity. Like Bcl-2, Bim possesses a hydrophobic C-terminus and localizes to intracytoplasmic membranes. Three Bim isoforms, probably generated by alternative splicing, all induce apoptosis, the shortest being the most potent. Wild-type Bcl-2 associates with Bim in vivo and modulates its death function, whereas Bcl-2 mutants that lack survival function do neither. Significantly, Bcl-xL and Bcl-w, the two closest homologues of Bcl-2, also bind to Bim and inhibit its activity, but more distant viral homologues, adenovirus E1B19K and Epstein-Barr virus BHRF-1, can do neither. Hence, Bim appears to act as a 'death ligand' which can only neutralize certain members of the pro-survival Bcl-2 sub-family.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis* / drug effects
  • Apoptosis* / genetics
  • Bcl-2-Like Protein 11
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Carrier Proteins / toxicity
  • Cell Line
  • Cysteine Endopeptidases / physiology
  • Cytoplasm / metabolism
  • Humans
  • Intracellular Membranes / metabolism
  • Membrane Proteins*
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins, Viral / antagonists & inhibitors
  • Oncogene Proteins, Viral / metabolism
  • Proteins / antagonists & inhibitors
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Proto-Oncogene Proteins*
  • Tumor Cells, Cultured
  • bcl-X Protein


  • Apoptosis Regulatory Proteins
  • BCL2L1 protein, human
  • BCL2L11 protein, human
  • BCL2L2 protein, human
  • Bcl-2-Like Protein 11
  • Bcl2l1 protein, mouse
  • Bcl2l11 protein, mouse
  • Bcl2l2 protein, mouse
  • Carrier Proteins
  • Membrane Proteins
  • Oncogene Proteins, Viral
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Cysteine Endopeptidases

Associated data

  • GENBANK/AF032457
  • GENBANK/AF032458
  • GENBANK/AF032459
  • GENBANK/AF032460
  • GENBANK/AF032461