Abstract
The Bin1 gene encodes a c-Myc-interacting adapter protein with tumor suppressor and cell death properties. In this study, we offer evidence that Bin1 participates in a mechanism through which c-Myc activates programmed cell death in transformed primary chick or rat cells. Antisense or dominant inhibitory Bin1 genes did not affect the ability of c-Myc to drive proliferation or transformation, but they did reduce the susceptibility of cells to c-Myc-induced apoptosis. Protein-protein interaction was implicated, suggesting that Bin1 mediates a death or death sensitization signal from c-Myc. Our findings offer direct support for the "dual signal" model of Myc apoptotic function, based on interactions with a binding protein. Loss of Bin1 in human tumors may promote malignant progression in part by helping to stanch the death penalty associated with c-Myc activation.
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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Adaptor Proteins, Signal Transducing
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Animals
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Apoptosis / physiology*
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cell Transformation, Neoplastic* / genetics
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Cell Transformation, Neoplastic* / pathology
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Chick Embryo
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Epithelial Cells / pathology
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Epithelial Cells / physiology
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Fibroblasts / pathology
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Gene Expression Regulation
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Genes, myc / genetics
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Genes, myc / physiology
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Humans
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Kidney / pathology
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Kidney / physiology
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Nuclear Proteins / genetics
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Nuclear Proteins / physiology*
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Proto-Oncogene Proteins c-myc / biosynthesis
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Proto-Oncogene Proteins c-myc / genetics
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Proto-Oncogene Proteins c-myc / physiology*
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Rats
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Reverse Transcriptase Polymerase Chain Reaction
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Transgenes
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Tumor Suppressor Proteins*
Substances
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Adaptor Proteins, Signal Transducing
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BIN1 protein, human
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Carrier Proteins
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Nuclear Proteins
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Proto-Oncogene Proteins c-myc
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Tumor Suppressor Proteins