Bax inhibitor-1, a mammalian apoptosis suppressor identified by functional screening in yeast

The mammalian proapoptotic protein Bax confers a lethal phenotype when expressed in yeast. By exploiting this phenotype, we have identified a novel human Bax inhibitor, Bl-1. Bl-1 is an evolutionarily conserved integral membrane protein containing multiple membrane-spanning segments and is predominantly localized to intracellular membranes, similar to Bcl-2 family proteins. Moreover, Bl-1 can interact with Bcl-2 and Bcl-X-L but not Bax or Bak, as demonstrated by in vivo cross-linking and coimmunoprecipitation studies. When overexpressed in mammalian cells, Bl-1 suppressed apoptosis induced by Bax, etoposide, staurosporine, and growth factor deprivation, but not by Fas (CD95). Conversely, Bl-1 antisense induced apoptosis. Bl-1 thus represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax.