Induction of cell death in murine fibroblasts by a c-myc promoter binding protein

R B Ray1

  • 1Department of Internal Medicine, Saint Louis University, Missouri 63110, USA.

Cell Growth & Differentiation : the Molecular Biology Journal of the American Association for Cancer Research
|September 1, 1995
PubMed

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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