The secretable form of trimeric TRAIL, a potent inducer of apoptosis.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane cytokine molecule of the TNF family. Soluble recombinant TRAIL has been shown to induce apoptosis in a wide variety of cancer cells in vitro and to specifically limit tumor growth without damaging normal cells and tissues in vivo. These results suggest a strong potential of TRAIL as an anticancer therapy. Here we report an artificial TRAIL gene that expresses and secretes trimeric TRAIL into the culture supernatant. This novel TRAIL gene is composed of three functional elements, including a secretion signal, a trimerization domain, and an apoptosis-inducing moiety of TRAIL gene sequence. The expression vectors delivering this TRAIL gene produced secretable forms of trimeric TRAIL proteins. These TRAIL proteins showed greater apoptotic activity than the known TRAIL protein that does not contain an additional trimerization domain. Our data suggest that the gene therapy using our artificial TRAIL gene may be used as an anticancer therapy.
Kim
Mi-Hyang
MH
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Billiar
Timothy R
TR
Seol
Dai-Wu
DW
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D015316:Genetic Therapy; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000628:therapy; D021382:Protein Sorting Signals / Q000235:genetics; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051017:Apoptosis Regulatory Proteins; D008562:Membrane Glycoproteins; D021382:Protein Sorting Signals; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha