title: Association of TRAF2 with the short form of cellular FLICE-like inhibitory protein prevents TNFR1-mediated apoptosis.
abstract: BACKGROUND
  We have previously shown that c-FLIPL is a more potent inhibitor than c-FLIPS of Fas ligand-induced apoptosis and that c-FLIPL physically binds to Daxx, an alternative Fas-signaling adaptor. Here we examined whether c-FLIPS effectively inhibits TNFR1-mediated apoptosis and triggers JNK activation through its interaction with TRAF2.
  
  
  RESULTS
  Some cancer cell lines, such as DU145, AGS, and PC3, have higher levels of c-FLIPS than other cell lines, such as SNU-719 and T24. The expression of c-FLIPS correlated with the susceptibility to TNFR1-mediated apoptosis. In contrast to DU145 and PC3, which are resistant to TNFR1-mediated apoptosis, T24 and SNU719 were sensitive to TNF-alpha treatment. To address the role of c-FLIPS in TNFR1-mediated apoptosis, we examined the molecular interaction between c-FLIPS and TRAF2. As expected, western blot analysis revealed that TRAF2 antibody immunoprecipitated a greater amount of c-FLIPS than c-FLIPL. Also, we measured the involvement of c-FLIPS in TNF-alpha-induced JNK activation and apoptosis by comparing these in TNF-alpha-resistant and TNF-alpha-sensitive cell lines. Treatment with TNF-alpha increased the phosphorylated JNK level in SNU719 and T24 cells, whereas DU145 and AGS cells were resistant to TNF-alpha-mediated apoptosis.
  
  
  CONCLUSIONS
  We now report that the short form of c-FLIPS is a more efficient inhibitor of TNF-receptor 1-mediated apoptosis signaling than the long form of the protein.
authors.affiliation: Center for Genome Sciences, National Institute of Health in Korea (KNIH), Nokbun-dong 5, Eunpyung-Gu, Seoul 122-701, Korea. youngyk@nih.go.kr.
authors.forename: Dong-Joon
authors.initials: DJ
authors.lastname: Kim
authors.forename: Chan
authors.initials: C
authors.lastname: Park
authors.forename: Bermseok
authors.initials: B
authors.lastname: Oh
authors.forename: Young-Youl
authors.initials: YY
authors.lastname: Kim