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J. Biol. Chem., Vol. 278, Issue 19, 16952-16956, May 9, 2003
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From the UPRES-EA 1033, IFR 118, Université des Sciences et
Technologies de Lille, Villeneuve d'Ascq 59655, France
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-
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*
,
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.
*
This work was supported by grants from the Ligue
Nationale Contre le Cancer (Comité du Pas-de-Calais), the French
Ministry of Research and Education, and the Genopole of Lille.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by a fellowship from the "Région Nord
Pas-de-Calais" and the "Ligue Nationale Contre le Cancer,
comité départemental."
§
Recipient of an Association pour la Recherche sur le Cancer (ARC)
fellowship. Present address: UMR-CNRS 6061, Université de Rennes
1, 34043 Rennes Cedex, France.
¶
To whom correspondence should be addressed: UPRES-EA 1033, Bâtiment SN3, Université des Sciences et Technologies de
Lille, 59655 Villeneuve d'Ascq, France. Tel.: 33-3-20-43-40-97; Fax: 33-3-20-43-40-38; E-mail: hubert.hondermarck@univ-lille1.fr.
Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
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