Multiple Bcl-2 family members demonstrate selective dimerizations with Bax.
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. Bax also heterodimerizes with Bcl-xL, Mcl-1, and A1. A Gly-159-->Ala substitution in BH1 of Bcl-xL 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.
Sedlak
T W
TW
Department of Medicine and Pathology, Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
Oltvai
Z N
ZN
Yang
E
E
Wang
K
K
Boise
L H
LH
Thompson
C B
CB
Korsmeyer
S J
SJ
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D017209:Apoptosis; D002460:Cell Line; D003001:Cloning, Molecular; D017124:Conserved Sequence; D006224:Cricetinae / Q000276:immunology; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells; D007377:Interleukin-3 / Q000494:pharmacology; D046911:Macromolecular Substances; D051379:Mice / Q000276:immunology; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011518:Proto-Oncogene Proteins / Q000737:chemistry* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D014162:Transfection; D051028:bcl-2-Associated X Protein; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000378:metabolism
D000911:Antibodies, Monoclonal; C494827:Bax protein, mouse; D007377:Interleukin-3; D046911:Macromolecular Substances; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051028:bcl-2-Associated X Protein; D001616:beta-Galactosidase; D019204:GTP-Binding Proteins