Bin1 mediates apoptosis by c-Myc in transformed primary cells

The Bin1 gene encodes a c-Myc-interacting adapter protein with tumor suppre ssor and cell death properties, In this study, we offer evidence that Bin1 participates in a mechanism through which c-Myc activates programmed cell d eath in transformed primary chick or rat cells. Antisense or dominant inhib itory 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-My c-induced apoptosis, Protein-protein interaction was implicated, suggesting that Bin1 mediates a death or death sensitization signal from c-Myc. Our f indings offer direct support for the "dual signal" model of Myc apoptotic f unction, based on interactions with a binding protein. Loss of Bin1 in huma n tumors may promote malignant progression in part by helping to stanch the death penalty associated with c-Myc activation.