Abstract
Using a protein interaction cloning technique, we identified cDNAs that encode a novel Bcl-2-binding protein, termed BAG-1. The BAG-1 protein shares no significant homology with Bcl-2 or other Bcl-2 family proteins, which can form homo- and heterodimers. In gene transfer experiments using a human lymphoid cell line, Jurkat, coexpression of BAG-1 and Bcl-2 provided markedly increased protection from cell death induced by several stimuli, including staurosporine, anti-Fas antibody, and cytolytic T cells, relative to cells that contained gene transfer-mediated elevations in either BAG-1 or Bcl-2 protein alone. BAG-transfected 3T3 fibroblasts also exhibited prolonged cell survival in response to an apoptotic stimulus. The findings indicate that bag-1 represents a new type of anti-cell death gene and suggest that some routes of apoptosis induction previously ascribed to Bcl-2-independent pathways may instead reflect a need for the combination of Bcl-2 and BAG-1.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Alkaloids / pharmacology
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Amino Acid Sequence
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Animals
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Carrier Proteins / blood
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Carrier Proteins / chemistry
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Carrier Proteins / metabolism*
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Cell Death / physiology*
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Cell Line
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Cell Survival / drug effects
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Cloning, Molecular
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DNA-Binding Proteins
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Gene Library
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Humans
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Kinetics
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Mice
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Molecular Sequence Data
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Protein Binding
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-bcl-2
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Radiation-Sensitizing Agents / pharmacology
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Recombinant Fusion Proteins / biosynthesis
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / isolation & purification
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Staurosporine
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Substrate Specificity
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Transcription Factors
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Transfection
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Tumor Cells, Cultured
Substances
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Alkaloids
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BCL2-associated athanogene 1 protein
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Carrier Proteins
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Radiation-Sensitizing Agents
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Recombinant Fusion Proteins
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Transcription Factors
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Staurosporine