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

Mol Cell. 1998 Feb;1(3):337-46. doi: 10.1016/s1097-2765(00)80034-9.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • COS Cells
  • Carcinogens / pharmacology
  • DNA, Antisense / pharmacology
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Etoposide / pharmacology
  • Fibroblasts / chemistry
  • Fibroblasts / metabolism
  • Fibroblasts / physiology
  • Gene Expression Regulation, Fungal
  • Gene Library
  • Genetic Testing / methods*
  • Growth Substances / pharmacology
  • Humans
  • Intracellular Membranes / chemistry
  • Mammals
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Molecular Sequence Data
  • Phenotype
  • Proteins*
  • Proto-Oncogene Proteins / antagonists & inhibitors*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Sequence Homology, Amino Acid
  • Staurosporine / pharmacology
  • Transfection
  • Yeasts / genetics
  • bcl-2-Associated X Protein
  • fas Receptor / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • BAX protein, human
  • Carcinogens
  • DNA, Antisense
  • DNA, Complementary
  • Growth Substances
  • Membrane Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • TMBIM6 protein, human
  • bcl-2-Associated X Protein
  • fas Receptor
  • Etoposide
  • Staurosporine