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, BI-1. BI-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, BI-1 can interact with Bcl-2 and Bcl-XL but Bax or Bak, as demonstrated by in vivo cross-linking and coimmunoprecipitation studies. When overexpressed in mammalian cells, BI-1 suppressed apoptosis included by Bax, etoposide, staurosporine, and growth factor deprivation, but not by Fas (CD95). Conversely, BI-1 antisense induced apoptosis. BI-1 thus represents a new type of regulator of cell death pathways controlled by Bcl-2 and Bax.
Xu
Q
Q
Burnham Institute Program on Apoptosis and Cell Death Research La Jolla, California 92037, USA.
Reed
J C
JC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D019556:COS Cells; D002273:Carcinogens / Q000494:pharmacology; D016373:DNA, Antisense / Q000494:pharmacology; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005047:Etoposide / Q000494:pharmacology; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D015966:Gene Expression Regulation, Fungal; D015723:Gene Library; D005820:Genetic Testing / Q000379:methods*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry; D008322:Mammals; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010641:Phenotype; D011506:Proteins; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection; D015003:Yeasts / Q000235:genetics; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D002273:Carcinogens; D016373:DNA, Antisense; D018076:DNA, Complementary; D006133:Growth Substances; D008565:Membrane Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C484209:TMBIM6 protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D005047:Etoposide; D019311:Staurosporine