J Biol Chem. 2003 May 9;278(19):16952-6. Epub 2003 Feb 25.

Tumor necrosis factor receptor-associated death domain protein is involved in the neurotrophin receptor-mediated antiapoptotic activity of nerve growth factor in breast cancer cells.External

El Yazidi-Belkoura, I., Adriaenssens, E., Dolle, L., Descamps, S., Hondermarck, H.,
--- - UPRES-EA 1033, IFR 118, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq 59655, France.
The common neurotrophin receptor p75(NTR) has been shown to initiate intracellular signaling that leads either to cell survival or to apoptosis depending on the cell type examined; however, the mechanism by which p75(NTR) initiates its intracellular transduction remains unclear. We show here that the tumor necrosis factor receptor-associated death domain protein (TRADD) interacts with p75(NTR) upon nerve growth factor (NGF) stimulation. TRADD could be immunodetected after p75(NTR) immunoprecipitation from MCF-7 breast cancer cells stimulated by nerve growth factor. In addition, confocal microscopy indicated that NGF stimulation induced the plasma membrane localization of TRADD. Using a dominant negative form of TRADD, we also show that interactions between p75(NTR) and TRADD are dependent on the death domain of TRADD, thus demonstrating its requirement for binding. Furthermore, the p75(NTR)-mediated activation of NF-kappaB was inhibited by transfection with a dominant negative TRADD, resulting in an inhibition of NGF antiapoptotic activity. These results thus demonstrate that TRADD is involved in the p75(NTR)-mediated antiapoptotic activity of NGF in breast cancer cells.
PMID: 12604596External
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 NGFR Link TRADD Co-Immunofluorescence staining MCF-7 12604596
DD NGFR Link TRADD Co-immunoprecipitation MCF-7 12604596
(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
Functional Role
Family DD1 DD2 Method Death-related Death-unrelated Reference
DD NGFR Link TRADD Co-Immunofluorescence staining NF-kB activation 12604596
(Link: click this icon to show interactions only between the two corresponding DDs)