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 from a human cervical carcinoma cell (HeLa) cDNA expression library (R. Ray and D. M. Miller, Mol. Cell. Biol., 11: 2154-2161, 1991). This study demonstrated that MBP-1 binds to the mouse c-myc P2 TATA box sequences and exerts a negative regulatory role on c-myc transcription. The role of MBP-1 on cell growth was initially examined by transfection of fibroblast cells with MBP-1 cDNA and resulted in rapid cell death. Subsequently, MBP-1 cDNA bearing an inducible promoter was introduced in murine fibroblast cells (NIH3T3) to control the expression of the exogenous MBP-1. Upon induction of exogenous MBP-1 expression, stable transfectants showed reduced c-myc expression, cell death, and DNA fragmentation. To further analyze whether c-myc inhibition mediates or complements the effect of MBP-1, the exogenous MBP-1 when introduced into NIH3T3 cells expressing deregulated human c-myc gene, cell death was interrupted. This study suggested that exogenous expression of MBP-1 induces cell death in fibroblasts by blocking cell proliferation.