Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity.
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.
La Jolla Cancer Research Foundation, California 92037.
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Takayama
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Sato
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Krajewski
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Kochel
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Irie
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Millan
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Reed
D016475:3T3 Cells; D000470:Alkaloids / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D019311:Staurosporine; D013379:Substrate Specificity; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D000470:Alkaloids; C091732:BCL2-associated athanogene 1 protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011838:Radiation-Sensitizing Agents; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D019311:Staurosporine