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c-myc Promoter Binding Protein Regulates the Cellular Response to an Altered Glucose Concentration

2007; American Chemical Society; Volume: 46; Issue: 29 Linguagem: Inglês

10.1021/bi7003558

1943-295X

Kara C. Sedoris, Shelia D. Thomas, Donald M. Miller,

S100 Proteins and Annexins

Alpha-enolase is a bifunctional gene encoding both a glycolytic enzyme and a DNA binding protein, c-myc binding protein (MBP-1). MBP-1 binds the c-myc promoter and downregulates c-myc transcription. Since these alpha-enolase gene products have important functions in glucose metabolism and growth regulation, this gene may play a central role in regulating the abnormal proliferative characteristics of transformed cells. To determine the role of alpha-enolase and MBP-1 in the cellular response to altered exogenous glucose concentration, MCF-7 cells were cultured in low (1 nM), physiological (5 mM), or high (25 mM) levels of glucose. Levels of alpha-enolase, MBP-1, and c-myc expression were compared to levels of cell proliferation and lactate production. At all glucose concentrations, MCF-7 cells demonstrated an initial increase in MBP-1 expression and a parallel decrease in c-myc transcript levels, which were accompanied by decreased proliferation. Cells grown in low glucose maintained the increased MBP-1 expression through 48 h, resulting in persistently lower rates of proliferation. However, physiologic or high glucose levels resulted in decreased MBP-1 expression, which was associated with increased cellular proliferation and lactate production. In these cells, c-myc mRNA returned to control levels as MBP-1 expression decreased. Cells grown in low glucose demonstrated a dramatic increase in c-myc mRNA at 48 h, which was associated with a loss in c-myc P2 promoter binding by MBP-1. This suggests that post-translational modifications of MBP-1 likely alter its DNA binding activity. These results demonstrate an important role for MBP-1 in the altered cell proliferation and energy utilization that occur in response to an altered glucose concentration.