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.
Mesh Terms:
Amino Acid Sequence, Animals, COS Cells, Cell Death, Cloning, Molecular, Humans, Jurkat Cells, Ligands, Membrane Proteins, Molecular Sequence Data, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factor Ligand Superfamily Member 13, Tumor Necrosis Factor-alpha
Cancer Res.
Date: Feb. 15, 2000
Download Curated Data For This Publication
3182
Switch View:
  • Interactions 4