TI  - A newly identified member of tumor necrosis factor receptor superfamily
      ( <prot>TR6</prot> ) suppresses  <prot>LIGHT</prot> -mediated apoptosis.
PG  - 13733-6
AB  - <prot>TR6</prot> (<prot>decoy receptor 3</prot> (<prot>DcR3</prot>)) is a new member of the tumor necrosis factor
      receptor (TNFR) family. <prot>TR6</prot> mRNA is expressed in lung tissues and colon
      adenocarcinoma, SW480. In addition, the expression of <prot>TR6</prot> mRNA was shown
      in the endothelial cell line and induced by phorbol 12-myristate
      13-acetate/ionomycin in Jurkat T leukemia cells. The open reading frame of
      <prot>TR6</prot> encodes 300 amino acids with a 29-residue signal sequence but no
      transmembrane region. Using histidine-tagged recombinant <prot>TR6</prot>, we screened
      soluble forms of TNF-ligand proteins with immunoprecipitation. Here, we
      demonstrate that  <prot>TR6</prot>   specifically binds two cellular ligands,  <prot>LIGHT</prot>
      (<prot>herpes virus entry mediator (HVEM)-L</prot>)  and  <prot><prot>Fas</prot> ligand</prot> (<prot>FasL</prot>/<prot>CD95L</prot> ). These
      bindings were confirmed with HEK 293 EBNA cells transfected with <prot>LIGHT</prot>
      cDNA by flow cytometry. <prot>TR6</prot> inhibited <prot>LIGHT</prot>-induced cytotoxicity in HT29
      cells. It has been shown that <prot>LIGHT</prot> triggers apoptosis of various tumor
      cells including HT29 cells that express both <prot><prot>lymphotoxin beta</prot> receptor</prot>
      (<prot>LTbetaR</prot>) and <prot>HVEM</prot>/<prot>TR2</prot> receptors. Our data suggest that <prot>TR6</prot> inhibits the
      interactions of   <prot>LIGHT</prot>   with  <prot>HVEM</prot>/<prot>TR2</prot>  and  <prot>LTbetaR</prot> , thereby suppressing
      <prot>LIGHT</prot>- mediated HT29 cell death. Thus, <prot>TR6</prot> may play a regulatory role for
      suppressing in <prot>FasL</prot>- and <prot>LIGHT</prot>-mediated cell death.
AD  - Department of Microbiology and Immunology and Walther Oncology Center,
