Promoter of TRAIL-R2 gene

Vitam Horm. 2004;67:35-49. doi: 10.1016/S0083-6729(04)67003-8.

Abstract

TRAIL-R2 promoter does not have a typical TATA-box but two functional Sp1-binding sites. TRAIL-R2 promoter belongs to the class of TATA-less and GC-box-containing promoters. The minimal promoter element is contained in the region spanning -198 to -116 upstream of translational initiation codon ATG. Computer analysis shows putative transcription factor binding sites such as c-Ets, AML-1a, c-Myb, Sp1, and GATA-1 in TRAIL-R2 promoter. Hypermethylation of TRAIL-R2 is not frequent compared with that of TRAIL-R3 and TRIAL-R4. There are no potential transcription factor binding sites in highly homologous regions between TRAIL-R2 promoter and TRAIL-R1 promoter, or between TRAIL-R2 promoter and mouse homologue mouse killer (MK) promoter. TRAIL-R2 is known to be a downstream gene of p53, a tumor-suppressor gene, and a p53-binding site in TRAIL-R2 intron 1 is responsible for p53-dependent transcription. Thapsigargin, endoplasmic reticulum Ca(2+)-ATPase inhibitor calcium releaser, upregulates TRAIL-R2 expression via the promoter region. Many regulators of TRAIL-R2 have been reported. However, it has not been demonstrated whether they regulate TRAIL-R2 via the promoter region. Here, we show a list of these regulators. Finally, we demonstrate the possibility of cancer therapy using regulation of TRAIL-R2 promoter.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Calcium / physiology
  • DNA / chemistry
  • DNA Methylation
  • Gene Expression / drug effects
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neoplasms / drug therapy
  • Promoter Regions, Genetic / genetics*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics*
  • Sequence Alignment
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / pharmacology

Substances

  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNFRSF10B protein, human
  • Tnfrsf10b protein, mouse
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • DNA
  • Calcium