Multiple Bcl-2 family members demonstrate selective dimerizations with Bax

Thomas W. Sedlak; Zoltán N. Oltvai; Elizabeth Yang; Kun Wang; Lawrence H. Boise; Craig B. Thompson; Stanley J. Korsmeyer

doi:10.1073/pnas.92.17.7834

Multiple Bcl-2 family members demonstrate selective dimerizations with Bax

Thomas W. Sedlak, Zoltán N. Oltvai, Elizabeth Yang, Kun Wang, Lawrence H. Boise, Craig B. Thompson, Stanley J. Korsmeyer

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Abstract

A family of Bcl-2-related proteins regulates cell death and shares highly conserved BH1 and BH2 domains. BH1 and BH2 domains of Bcl-2 were required for it to heterodimerize with Bax and to repress apoptosis. A yeast two-hybrid assay accurately reproduced this interaction and defined a selectivity and hierarchy of further dimerizations. Bat also heterodimerizes with Bcl-x(L), Mcl-1, and A1. A Gly-159 → Ala substitution in BH1 of Bcl-x(L) disrupted its heterodimerization with Bax and abrogated its inhibition of apoptosis in mammalian cells. This suggests that the susceptibility to apoptosis is determined by multiple competing dimerizations in which Bax may be a common partner.

Original language	English (US)
Pages (from-to)	7834-7838
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	92
Issue number	17
DOIs	https://doi.org/10.1073/pnas.92.17.7834
State	Published - Aug 15 1995
Externally published	Yes

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title = "Multiple Bcl-2 family members demonstrate selective dimerizations with Bax",

abstract = "A family of Bcl-2-related proteins regulates cell death and shares highly conserved BH1 and BH2 domains. BH1 and BH2 domains of Bcl-2 were required for it to heterodimerize with Bax and to repress apoptosis. A yeast two-hybrid assay accurately reproduced this interaction and defined a selectivity and hierarchy of further dimerizations. Bat also heterodimerizes with Bcl-x(L), Mcl-1, and A1. A Gly-159 → Ala substitution in BH1 of Bcl-x(L) disrupted its heterodimerization with Bax and abrogated its inhibition of apoptosis in mammalian cells. This suggests that the susceptibility to apoptosis is determined by multiple competing dimerizations in which Bax may be a common partner.",

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AU - Sedlak, Thomas W.

AU - Oltvai, Zoltán N.

AU - Yang, Elizabeth

AU - Wang, Kun

AU - Boise, Lawrence H.

AU - Thompson, Craig B.

AU - Korsmeyer, Stanley J.

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AB - A family of Bcl-2-related proteins regulates cell death and shares highly conserved BH1 and BH2 domains. BH1 and BH2 domains of Bcl-2 were required for it to heterodimerize with Bax and to repress apoptosis. A yeast two-hybrid assay accurately reproduced this interaction and defined a selectivity and hierarchy of further dimerizations. Bat also heterodimerizes with Bcl-x(L), Mcl-1, and A1. A Gly-159 → Ala substitution in BH1 of Bcl-x(L) disrupted its heterodimerization with Bax and abrogated its inhibition of apoptosis in mammalian cells. This suggests that the susceptibility to apoptosis is determined by multiple competing dimerizations in which Bax may be a common partner.

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Multiple Bcl-2 family members demonstrate selective dimerizations with Bax

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