Cell. 1996 Jan 26;84(2):299-308.

TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways.External

Hsu, H., Shu, H. B., Pan, M. G., Goeddel, D. V.,
--- - Tularik, Incorporated, South San Francisco, California 94080, USA.
Tumor necrosis factor (TNF) can induce apoptosis and activate NF-kappa B through signaling cascades emanating from TNF receptor 1 (TNFR1). TRADD is a TNFR1-associated signal transducer that is involved in activating both pathways. Here we show that TRADD directly interacts with TRAF2 and FADD, signal transducers that activate NF-kappa B and induce apoptosis, respectively. A TRAF2 mutant lacking its N-terminal RING finger domain is a dominant-negative inhibitor of TNF-mediated NF-kappa B activation, but does not affect TNF-induced apoptosis. Conversely, a FADD mutant lacking its N-terminal 79 amino acids is a dominant-negative inhibitor of TNF-induced apoptosis, but does not inhibit NF-kappa B activation. Thus, these two TNFR1-TRADD signaling cascades appear to bifurcate at TRADD.
PMID: 8565075External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vitro interaction
  DD1 DD2 Reference
Family DD1 DD2 Method Species Region Expression Species Region Expression
DD FADD Link TRADD Yeast two-hybrid Not specified Full length Yeast Not specified Full length Yeast 8565075
DD FADD Link TRADD Yeast two-hybrid Not specified Full length Yeast Not specified 55-312 Yeast 8565075
DD FADD Link TRADD Yeast two-hybrid Not specified Full length Yeast Not specified 195-312 Yeast 8565075
(Link: click this icon to show interactions only between the two corresponding DDs)
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
  Endogenous
expression
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
DD FADD Link TRADD Co-immunoprecipitation HEK293 Not specified Full length Not specified Full length 8565075
DD TNFR1 Link TRADD Co-immunoprecipitation U937 8565075
(Link: click this icon to show interactions only between the two corresponding DDs)