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Published on: June 29, 2011
Induction of cell death in murine fibroblasts by a c-myc promoter binding protein
1Department of Internal Medicine, Saint Louis University, Missouri 63110, USA.
Abstract:
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.
Insights
The c-myc promoter binding protein (MBP-1) inhibits c-myc transcription and fibroblast proliferation. Overexpression of MBP-1 in cells leads to cell death, suggesting a role in blocking cell growth.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- The c-myc promoter binding protein (MBP-1) was previously identified from a human cervical carcinoma cell (HeLa) cDNA expression library.
- MBP-1 binds to the mouse c-myc P2 TATA box sequences, indicating a role in regulating c-myc transcription.
Purpose of the Study:
- To investigate the role of MBP-1 in cell growth and proliferation.
- To determine if c-myc inhibition mediates the effects of MBP-1 on cell death.
Main Methods:
- Transfection of fibroblast cells with MBP-1 cDNA.
- Introduction of MBP-1 cDNA with an inducible promoter into murine fibroblast cells (NIH3T3).
- Analysis of c-myc expression, cell death, and DNA fragmentation upon MBP-1 induction.
Main Results:
- Exogenous MBP-1 expression in NIH3T3 cells resulted in reduced c-myc expression, cell death, and DNA fragmentation.
- MBP-1 binding to the c-myc P2 TATA box negatively regulates c-myc transcription.
- Cell death was interrupted when MBP-1 was introduced into cells expressing a deregulated human c-myc gene, suggesting c-myc inhibition is key.
Conclusions:
- Exogenous expression of MBP-1 induces cell death in fibroblasts.
- MBP-1 exerts its effect by blocking cell proliferation through the inhibition of c-myc transcription.
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