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Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death

Identifieur interne : 004591 ( Main/Exploration ); précédent : 004590; suivant : 004592

Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programed cell death

Auteurs : Zoltán N. Oltval [États-Unis] ; Curt L. Milliman [États-Unis] ; Stanley J. Korsmeyer [États-Unis]

Source :

RBID : ISTEX:1B31A4D63603B8AFFF0532E3BE6C6E162A18B1AA

English descriptors

Abstract

Abstract: Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (α) and two forms of cytosolic protein (β and γ). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.

Url:
DOI: 10.1016/0092-8674(93)90509-O


Affiliations:


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Le document en format XML

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<term>3fll</term>
<term>Acad</term>
<term>Acid homology</term>
<term>Acid sequence</term>
<term>Alternative transcripts</term>
<term>Amino</term>
<term>Amino acid</term>
<term>Amino acid residues</term>
<term>Amino acid sequence</term>
<term>Amino acids</term>
<term>Apoptosis</term>
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<term>Apoptotic cell death</term>
<term>Apoptotic death</term>
<term>Apoptotic stimulus</term>
<term>Baxa</term>
<term>Bcl2</term>
<term>Cdna</term>
<term>Cdna library</term>
<term>Cdna probe</term>
<term>Cdna sequence</term>
<term>Cell cdna library</term>
<term>Cell death</term>
<term>Cell line</term>
<term>Cell lines</term>
<term>Cell lysates</term>
<term>Cell survival</term>
<term>Cells transfected</term>
<term>Chromosomal breakpoint</term>
<term>Clone</term>
<term>Clones transfected</term>
<term>Cold spring harbor</term>
<term>Cold spring harbor laboratory press</term>
<term>Comparable levels</term>
<term>Control antibody</term>
<term>Control cells</term>
<term>Control vector</term>
<term>Cortical thymocytes</term>
<term>Cyanogen bromide</term>
<term>Cytosolic</term>
<term>Cytosolic form</term>
<term>Death repressor activity</term>
<term>Death stimulus</term>
<term>Deprivation</term>
<term>Edman degradation</term>
<term>Endogenous</term>
<term>Endogenous baxa</term>
<term>Endogenous murine</term>
<term>Exon</term>
<term>Exon boundaries</term>
<term>Exon probe</term>
<term>Experimental procedures</term>
<term>Expression vector</term>
<term>Extensive homology</term>
<term>Fetal calf serum</term>
<term>First cycle</term>
<term>Follicular lymphoma</term>
<term>Forms heterodimers</term>
<term>Forms homodimers</term>
<term>Genetic control</term>
<term>Genomic</term>
<term>Glacial acetic acid</term>
<term>High levels</term>
<term>Hockenbery</term>
<term>Homodimers</term>
<term>Homology</term>
<term>Human cells</term>
<term>Human hamster</term>
<term>Immunoprecipitated</term>
<term>Immunoprecipitates</term>
<term>Integral membrane protein</term>
<term>Korsmeyer</term>
<term>Last cycle</term>
<term>Lymphoma</term>
<term>Lysates</term>
<term>Lysis buffer</term>
<term>Many adult tissues</term>
<term>Molecular mass</term>
<term>Murine</term>
<term>Murine baxa</term>
<term>Murine cdna</term>
<term>Natl</term>
<term>Negative selection</term>
<term>Northern blot analysis</term>
<term>Overexpressed</term>
<term>Partial protection</term>
<term>Peptide</term>
<term>Peptide fragments</term>
<term>Percent viability</term>
<term>Phage clone</term>
<term>Polymerase cetus</term>
<term>Primary immunoprecipitates</term>
<term>Primer</term>
<term>Primer pool</term>
<term>Proc</term>
<term>Protein</term>
<term>Protein partner</term>
<term>Protein products</term>
<term>Protein sequence</term>
<term>Repressor</term>
<term>Rescue cells</term>
<term>Restriction analysis</term>
<term>Secondary immunoprecipitation</term>
<term>Sequencing</term>
<term>Signal anchor sequence</term>
<term>Speciesspecific biotinylated</term>
<term>Spleen virus</term>
<term>Stably transfected cells</term>
<term>Standard protocol</term>
<term>Substantial amounts</term>
<term>Transfected</term>
<term>Transgenic mice</term>
<term>Transmembrane domain</term>
<term>Triplicate cultures</term>
<term>Tsujimoto</term>
<term>Unpublished data</term>
<term>Viability assays</term>
<term>Washington university</term>
<term>Western blot analysis</term>
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<div type="abstract" xml:lang="en">Abstract: Bcl-2 protein is able to repress a number of apoptotic death programs. To investigate the mechanism of Bcl-2's effect, we examined whether Bcl-2 interacted with other proteins. We identified an associated 21 kd protein partner, Bax, that has extensive amino acid homology with Bcl-2, focused within highly conserved domains I and II. Bax is encoded by six exons and demonstrates a complex pattern of alternative RNA splicing that predicts a 21 kd membrane (α) and two forms of cytosolic protein (β and γ). Bax homodimerizes and forms heterodimers with Bcl-2 in vivo. Overexpressed Bax accelerates apoptotic death induced by cytokine deprivation in an IL-3-dependent cell line. Overexpressed Bax also counters the death repressor activity of Bcl-2. These data suggest a model in which the ratio of Bcl-2 to Bax determines survival or death following an apoptotic stimulus.</div>
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