Résumé
The common neurotrophin receptor p75NTR 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 p75NTR initiates its intracellular transduction remains unclear. We show here that the tumor necrosis factor receptor-associated death domain protein (TRADD) interacts with p75NTR upon nerve growth factor (NGF) stimulation. TRADD could be immunodetected after p75NTR 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 p75NTR and TRADD are dependent on the death domain of TRADD, thus demonstrating its requirement for binding. Furthermore, the p75NTR-mediated activation of NF- B 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 p75NTR-mediated antiapoptotic activity of NGF in breast cancer cells.