Bin1 mediates apoptosis by c-Myc in transformed primary cells.
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.
DuHadaway
J B
JB
The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Sakamuro
D
D
Ewert
D L
DL
Prendergast
G C
GC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D002642:Chick Embryo; D004847:Epithelial Cells / Q000473:pathology / Q000502:physiology; D005347:Fibroblasts / Q000473:pathology; D005786:Gene Expression Regulation; D016259:Genes, myc / Q000235:genetics / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019076:Transgenes; D025521:Tumor Suppressor Proteins
D048868:Adaptor Proteins, Signal Transducing; C101410:BIN1 protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D025521:Tumor Suppressor Proteins