Regulation of the human TRAIL gene.
TRAIL is a member of the TNF superfamily that induces tumor-selective cell death by engaging the pro-apoptotic death receptors DR4 and DR5. The antitumor potential of the TRAIL pathway has been targeted by several therapeutic approaches including recombinant TRAIL and TRAIL-receptor agonist antibodies among others. Interest in sensitizing tumor cells to TRAIL-mediated apoptosis has driven investigations of TRAIL-receptor gene regulation, though regulation of the TRAIL gene has been less studied. Physiologically, TRAIL serves as a pro-apoptotic effector molecule in the immune surveillance of cancer that is conditionally expressed by immune cells upon stimulation via an interferon-response element that was identified in early studies of the TRAIL gene promoter. Here, we map the TRAIL gene promoter and review studies of TRAIL gene regulation that involve several modalities of gene regulation including transcription factors, epigenetics, single-nucleotide polymorphisms and functionally distinct isoforms.
Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Department of Medicine (Hematology/Oncology), Penn State Hershey Cancer Institute, Hershey, PA, USA.
Joshua E
JE
Allen
Wafik S
WS
El-Deiry
D017209:Apoptosis / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha