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

Xiao Ming Yin, Zoltán N. Oltvai, Stanley J. Korsmeyer

Research output: Contribution to journalArticle

1141 Citations (Scopus)

Abstract

BCL-2 was isolated from the t(14;18) chromosomal breakpoint in follicular B-cell lymphoma1-3. Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths4-13. An emerging family of Bcl-2 -related proteins share two highly conserved regions14-20 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-214. We report here that site-specific mutagenesis of Bcl-2 establishes the two domains as novel dimerization motifs. Substitution of Gly 145 in BHl domain or Trp 188 in BH2 domain completely abrogated Bcl-2's death-repressor activity in interleukin-3 deprivation, γ-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.

Original languageEnglish (US)
Pages (from-to)321-323
Number of pages3
JournalNature
Volume369
Issue number6478
DOIs
StatePublished - Jan 1 1994

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Apoptosis
Follicular Lymphoma
Interleukin-3
Dimerization
B-Cell Lymphoma
Site-Directed Mutagenesis
Glucocorticoids
Cell Survival
Mutation
Proteins

ASJC Scopus subject areas

  • General

Cite this

BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. / Yin, Xiao Ming; Oltvai, Zoltán N.; Korsmeyer, Stanley J.

In: Nature, Vol. 369, No. 6478, 01.01.1994, p. 321-323.

Research output: Contribution to journalArticle

Yin, Xiao Ming ; Oltvai, Zoltán N. ; Korsmeyer, Stanley J. / BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax. In: Nature. 1994 ; Vol. 369, No. 6478. pp. 321-323.
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