TI  -  <prot>TRADD</prot> - <prot>TRAF2</prot>  and  <prot>TRADD</prot> - <prot>FADD</prot>  interactions define two distinct <prot>TNF receptor 1</prot>
      signal transduction pathways.
PG  - 299-308
AB  -  Tumor necrosis factor (TNF)  can induce apoptosis and activate <prot>NF-kappa B </prot>
      through signaling cascades emanating from  <prot>TNF receptor 1</prot> (<prot>TNFR1</prot>) .  <prot>TRADD</prot>  is
      a  <prot>TNFR1</prot> -associated signal transducer that is involved in activating both
      pathways. Here we show that   <prot>TRADD</prot>   directly interacts with  <prot>TRAF2</prot>  and  <prot>FADD</prot> ,
      signal transducers that activate <prot>NF-kappa B</prot> and induce apoptosis,
      respectively. A <prot>TRAF2</prot> mutant lacking its N-terminal RING finger domain is
      a dominant-negative inhibitor of TNF-mediated <prot>NF-kappa B</prot> activation, but
      does not affect TNF-induced apoptosis. Conversely, a <prot>FADD</prot> mutant lacking
      its N-terminal 79 amino acids is a dominant-negative inhibitor of
      TNF-induced apoptosis, but does not inhibit <prot>NF-kappa B</prot> activation. Thus,
      these two  <prot>TNFR1</prot> - <prot>TRADD</prot>  signaling cascades appear to bifurcate at <prot>TRADD</prot>.
AD  - Tularik, Incorporated, South San Francisco, California 94080, USA.
