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Bim: a novel member of the Bcl‐2 family that promotes apoptosis
Author(s) -
O'Connor Liam,
Strasser Andreas,
O'Reilly Lorraine A.,
Hausmann George,
Adams Jerry M.,
Cory Suzanne,
Huang David C.S.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.2.384
Subject(s) - biology , apoptosis , bcl 2 family , microbiology and biotechnology , family member , genetics , cancer research , computational biology , programmed cell death , genealogy , history
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‐x L 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.