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

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Citation

Yin XM, Oltvai ZN, Korsmeyer SJ

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

Nature. 1994 May 26;369(6478):321-3.

PubMed ID
8183370 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Apoptosis regulator Bcl-2P10415Details