Mut. Miyashita et al., Molecular cloning and characterization of six novel isoforms of human Bim,a member of the proapoptotic Bcl-2 family, FEBS LETTER, 509(1), 2001, pp. 135-141
Bim protein is one of the BH3-only proteins, members of the Bcl-2 family th
at have only one of the Bcl-2 homology regions, BH3. BH3-only proteins are
essential initiators Of apoptotic cell death. Thus far, three isoforms of B
im have been reported, i.e. Bim(EL), Bim(L) and Bim(s). Here we report the
cloning and characterization of six novel isoforms of human Bim, designated
as Bim alpha1, alpha2, and beta1-beta4, which are generated by alternative
splicing. Unlike the three known isoforms, none of these novel isoforms co
ntained a C-terminal hydrophobic region. Among the novel isoforms, only Bim
alpha1 and alpha2 contained a BH3 domain and were proapoptotic, although l
ess potent than the classical isoforms. These two isoforms localized, at le
ast in part, in mitochondria when transiently expressed in HeLa cells as a
green fluorescent protein-fused form. These results suggest that the BH3 do
main is necessary for induction of apoptosis and mitochondrial localization
but not sufficient for the full proapoptotic activity. While the classical
isoforms were always predominantly expressed in transformed cells, express
ion profiles of him isoforms were highly variable among normal tissues at l
east in humans, suggesting a tissue-specific transcriptional regulation of
bim. (C) 2001 Federation of European Biochemical Societies. Published by El
sevier Science B.V. All rights reserved.