BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax
Identifieur interne : 004362 ( Main/Exploration ); précédent : 004361; suivant : 004363BH1 and BH2 domains of Bcl-2 are required for inhibition of apoptosis and heterodimerization with Bax
Auteurs : Xiao-Ming Yin [États-Unis] ; Zoltn N. Oltvai [États-Unis] ; Stanley J. Korsmeyer [États-Unis]Source :
- Nature [ 0028-0836 ] ; 1994-05-26.
Abstract
BCL-2 was isolated from the t(14;18) chromosomal breakpoint in follicular B-cell lymphoma13. Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths413. An emerging family of Bcl-2 -related proteins share two highly conserved regions1420 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. Substitu-tion of Gly 145 in BHl domain or Trp 188 in BH2 domain completely abrogated Bcl-2's death-repressor activity in inter-leukin-3 deprivation, -irradiation and glucocorticoid-induced apoptosis. Mutations that affected Bcl-2's function also disrupted its heterodimerization with Bax, yet still permitted Bcl-2 homo-dimerization. These results establish a functional role for the BH1 and BH2 domains and suggest Bcl-2 exerts its action through heterodimerization with Bax.
Url:
DOI: 10.1038/369321a0
Affiliations:
- États-Unis
- Missouri (État)
- Saint-Louis (Missouri)
- École de médecine (Université Washington de Saint-Louis)
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Le document en format XML
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<front><div type="abstract">BCL-2 was isolated from the t(14;18) chromosomal breakpoint in follicular B-cell lymphoma13. Bcl-2 has the unique oncogenic role of extending cell survival by inhibiting a variety of apoptotic deaths413. An emerging family of Bcl-2 -related proteins share two highly conserved regions1420 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. Substitu-tion of Gly 145 in BHl domain or Trp 188 in BH2 domain completely abrogated Bcl-2's death-repressor activity in inter-leukin-3 deprivation, -irradiation and glucocorticoid-induced apoptosis. Mutations that affected Bcl-2's function also disrupted its heterodimerization with Bax, yet still permitted Bcl-2 homo-dimerization. These results establish a functional role for the BH1 and BH2 domains and suggest Bcl-2 exerts its action through heterodimerization with Bax.</div>
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