Identification of an additional hypoxia responsive element in the glyceraldehyde-3-phosphate dehydrogenase gene promoter

Using transient transfection experiments with the Glyceraldehyde-3-phosphate dehydrogenase promoter region linked to a luciferase reporter gene, we found that GAPDH was transcriptionally activated by hypoxia in each of three human prostate cancer cell lines tested, with the greatest level of induction in the most differentiated cell line

Shan Lu; Xiang Gu; Sara Hoestje; Daniel E. Epner

2002

Scholarcy highlights

  • Glyceraldehyde-3-phosphate dehydrogenase is a multifunctional enzyme overexpressed in many tumors and induced by hypoxia in normal and malignant cells
  • Using transient transfection experiments with the GAPDH promoter region linked to a luciferase reporter gene, we found that GAPDH was transcriptionally activated by hypoxia in each of three human prostate cancer cell lines tested, with the greatest level of induction in the most differentiated cell line
  • Using sequence analysis of the GAPDH promoter region, we identified a novel hypoxia responsive element distinct from the previously characterized one that consists of two consensus hypoxia inducible factor-1 sites arranged as inverted repeats separated by 5 bp
  • Heterologous promoter constructs containing only one or two copies of the novel HRE plus a minimal promoter consisting of a TATA box drove hypoxia inducible expression of the luciferase reporter gene in transient transfection assays
  • Mutation of HIF-1 sites within the novel HRE resulted in complete loss of function
  • Mutation of hypoxia inducible factor-1 sites within the novel hypoxia responsive element resulted in complete loss of function

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