BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax.

Abstract:

:Bcl-2 was isolated from the t(14;18) chromosomal breakpoint in follicular B-cell lymphoma. Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths. An emerging family of Bcl-2-related proteins share two highly conserved regions referred to here as Bcl-2 homology 1 and 2 (BH1 and BH2) domains (Fig. 1). This includes Bax which heterodimerizes with Bcl-2 and when overexpressed counteracts Bcl-2. We report here that site-specific mutagenesis of Bcl-2 establishes the two domains as novel dimerization motifs. Substitution of Gly 145 in BH1 domain or Trp 188 in BH2 domain completely abrogated Bcl-2's death-repressor activity in interleukin-3 deprivation, gamma-irradiation and glucocorticoid-induced apoptosis. Mutations that affected Bcl-2's function also disrupted its heterodimerization with Bax, yet still permitted Bcl-2 homodimerization. These results establish a functional role for the BH1 and BH2 domains and suggest Bcl-2 exerts its action through heterodimerization with Bax.

journal_name

Nature

journal_title

Nature

authors

Yin XM,Oltvai ZN,Korsmeyer SJ

doi

10.1038/369321a0

subject

Has Abstract

pub_date

1994-05-26 00:00:00

pages

321-3

issue

6478

eissn

0028-0836

issn

1476-4687

journal_volume

369

pub_type

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