Bim: a novel member of the Bcl-2 family that promotes apoptosis.
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.
O'Connor
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L
The Walter and Eliza Hall Institute of Medical Research, PO Royal Melbourne Hospital, Victoria, Australia.
Strasser
A
A
O'Reilly
L A
LA
Hausmann
G
G
Adams
J M
JM
Cory
S
S
Huang
D C
DC
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology* / Q000633:toxicity; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors / Q000378:metabolism; D011506:Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
D051017:Apoptosis Regulatory Proteins; C494811:BCL2L1 protein, human; C000606775:BCL2L11 protein, human; C491073:BCL2L2 protein, human; D000072224:Bcl-2-Like Protein 11; C494812:Bcl2l1 protein, mouse; C000606776:Bcl2l11 protein, mouse; C101155:Bcl2l2 protein, mouse; D002352:Carrier Proteins; D008565:Membrane Proteins; D009856:Oncogene Proteins, Viral; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D003546:Cysteine Endopeptidases