MULTIPLE BCL-2 FAMILY MEMBERS DEMONSTRATE SELECTIVE DIMERIZATIONS WITH BAX

A family of Bcl-2-related proteins regulates cell death and shares hig hly conserved BH1 and BH2 domains, BH1 and BH2 domains of Bcl-2 were r equired for it to heterodimerize with Bar and to repress apoptosis. A yeast two-hybrid assay accurately reproduced this interaction and defi ned a selectivity and hierarchy of further dinerizations, Bax also het erodimerizes with Bcl-x(L), Mcl-1, and A1. A Gly-159 --> Ala substitut ion in BH1 of Bcl-x(L), disrupted its heterodimerization with Bax and abrogated its inhibition of apoptosis in mammalian cells. This suggest s that the susceptibility to apoptosis is determined by multiple compe ting dimerizations in which Bax may be a common partner.