title: Myc tagging along the TRAIL to death receptor 5.
abstract: Tumor necrosis factor-related apoptosis inducing ligand (TRAIL; also known as Apo2L) is an apoptotic cytokine that is being developed as a novel anticancer agent. TRAIL mediates its effect via death receptors 4 (DR4) and DR5 and appears to selectively induce apoptosis in cancer cells. The molecular basis of why normal cells seem to better tolerate this novel cytokine remains unknown. Recently, it has been reported that Myc oncoprotein by upregulating DR5 appears to augment cellular susceptibility to TRAIL and to DR5 agonistic antibodies. Several previous studies have already established that various clinically relevant agents by upregulating DR5 sensitize cells to TRAIL. However, the finding that DR5 is upregulated by an oncoprotein that is overexpressed in several tumor types is noteworthy and may spark future investigations aiming to explore the Myc and DR5 expression status of primary tumors and their ultimate vulnerability to DR5-targeted therapeutics.
authors.affiliation: Department of Pharmacology, State University of New York, Syracuse 13210, USA. sheikhm@upstate.edu
authors.forename: M Saeed
authors.initials: MS
authors.lastname: Sheikh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C489427:MYC protein, human; D008562:Membrane Glycoproteins; D016271:Proto-Oncogene Proteins c-myc; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha