Promoter structure and transcription initiation sites of the human death receptor 5/TRAIL-R2 gene.

The death receptor 5 (DR5) is a receptor for tumor necrosis factor-related apoptosis-inducing ligand and is able to induce apoptosis in various tumor cells. The expression of DR5 is up-regulated at the transcriptional level by p53, genotoxic stress and so on. To investigate the structure of the DR5 gene promoter, we screened and sequenced a genomic clone containing the 5'-flanking region of the DR5 gene. RNase protection assays showed two major transcription start sites around -122 and -137 upstream of the translation initiation codon ATG. Transient transfections with serial 5'-deletion mutants identified the minimal promoter element spanning -198 to -116. Site-directed mutagenesis demonstrated that the DR5 gene promoter has no typical TATA-box, but has two Sp1 sites responsible for the basal transcription activity of the DR5 gene promoter.