c-myc promoter binding protein regulates the cellular response to an altered glucose concentration.
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.
Sedoris
Kara C
KC
James Graham Brown Cancer Center, University of Louisville, 529 South Jackson Street, Louisville, Kentucky 40202, USA.
Thomas
Shelia D
SD
Miller
Donald M
DM
D001665:Binding Sites; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D016259:Genes, myc; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C116115:MYCBP protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C095157:ENO1 protein, human; D010751:Phosphopyruvate Hydratase; D005947:Glucose