INDUCTION OF CELL-DEATH IN MURINE FIBROBLASTS BY A C-MYC PROMOTER-BINDING PROTEIN

The c-myc promoter binding protein (MBP-1) was identified previously f rom a human cervical carcinoma cell (HeLa) cDNA expression library (R. Ray and D. M. Miller, Mel. Cell. Biol., 11: 2154-2161, 1992). This st udy demonstrated that MEP-1 binds to the mouse c-myc P2 TATA box seque nces and exerts a negative regulatory role on c-myc transcription. The role of MBP-1 on cell growth was initially examined by transfection o f fibroblast cells with MBP-1 cDNA and resulted in rapid cell death. S ubsequently, MBP-1 cDNA bearing an inducible promoter was introduced i n murine fibroblast cells (NIH3T3) to control the expression of the ex ogenous MBP-1. Upon induction of exogenous MBP-1 expression, stable tr ansfectants showed reduced c-myc expression, cell death, and DNA fragm entation. To further analyze whether c-myc inhibition mediates or comp lements the effect of MBP-1, the exogenous MBP-1 when introduced into NIH3T3 cells expressing deregulated human c-myc gene, cell death was i nterrupted. This study suggested that exogenous expression of MBP-1 in duces cell death in fibroblasts by blocking cell proliferation.