APRIL/TRDL-1, a tumor necrosis factor-like ligand, stimulates cell death.
We have examined the activity of a new member of the tumor necrosis factor (TNF) family identified through Expressed Sequence Tag database searching using TNFalpha protein as the search query. We have termed this protein TNF-related death ligand-la (TRDL-1alpha). Traditional cDNA library screening identified two additional splice variants designated TRDL-1beta and TRDL-1gamma that differed from TRDL-1alpha by the deletion of two small regions within the protein coding region. TRDL-1alpha is identical in sequence to the recently described molecule, APRIL, that may induce cell proliferation. We found, however, that purified, FLAG-tagged TRDL-1alpha caused Jurkat cell death with kinetics that paralleled FasL. In vitro binding experiments demonstrated that TRDL-1alpha coprecipitated Fas and HVEM and suggested TRDL-1alpha as an alternate ligand for these receptors. TRDL-1 localized to chromosome 17p13.3 and its expression was widespread in normal tissues. Examination of 48 tumor samples revealed high levels of TRDL-1 expression in several tumors, including those from the gastrointestinal tract. Expression of TRDL-1 in COS-1 cells confirmed membrane association of TRDL-1, typical of TNF family members.
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The Huntsman Cancer Institute, Division of Molecular Pharmacology, Salt Lake City, Utah 84112, USA.
Manos
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Jensen
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Nadauld
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Jones
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D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D016923:Cell Death / Q000187:drug effects; D003001:Cloning, Molecular; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000378:metabolism*; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008024:Ligands; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C114631:TNFSF13 protein, human; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha