Promoter of TRAIL-R2 gene.
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.
Yoshida
Tatsushi
T
Department of Molecular-Targeting Cancer Prevention Graduate School of Medical Science, Kyoto Prefectural University of Medicine Kyoto 602-8566, Japan.
Sakai
Toshiyuki
T
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002118:Calcium / Q000502:physiology; D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy; D011401:Promoter Regions, Genetic / Q000235:genetics*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000494:pharmacology
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C505639:TNFRSF10B protein, human; C505640:Tnfrsf10b protein, mouse; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004247:DNA; D002118:Calcium