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
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Antineoplastic Agents, Phytogenic / pharmacology
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Apoptosis / drug effects
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Apoptosis / physiology*
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Apoptosis Regulatory Proteins
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COS Cells
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Carcinogens / pharmacology
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DNA, Antisense / pharmacology
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DNA, Complementary / analysis
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DNA, Complementary / genetics
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Etoposide / pharmacology
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Fibroblasts / chemistry
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Fibroblasts / metabolism
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Fibroblasts / physiology
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Gene Expression Regulation, Fungal
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Gene Library
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Genetic Testing / methods*
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Growth Substances / pharmacology
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Humans
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Intracellular Membranes / chemistry
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Mammals
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Membrane Proteins / analysis
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Molecular Sequence Data
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Phenotype
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Proteins*
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Proto-Oncogene Proteins / antagonists & inhibitors*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Sequence Homology, Amino Acid
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Staurosporine / pharmacology
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Transfection
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Yeasts / genetics
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bcl-2-Associated X Protein
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fas Receptor / genetics
Substances
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Antineoplastic Agents, Phytogenic
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Apoptosis Regulatory Proteins
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BAX protein, human
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Carcinogens
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DNA, Antisense
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DNA, Complementary
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Growth Substances
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Membrane Proteins
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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TMBIM6 protein, human
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bcl-2-Associated X Protein
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fas Receptor
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Etoposide
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Staurosporine