NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis

被引:235
作者
Salehi, AH
Roux, PP
Kubu, CJ
Zeindler, C
Bhakar, A
Tannis, LL
Verdi, JM
Barker, PA
机构
[1] McGill Univ, Montreal Neurol Inst, Ctr Neuronal Survival, Montreal, PQ H3A 2B4, Canada
[2] John P Robarts Res Inst, London, ON N6A 5K8, Canada
基金
英国医学研究理事会;
关键词
D O I
10.1016/S0896-6273(00)00036-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The mechanisms employed by the p75 neurotrophin receptor (p75NTR) to mediate neurotrophin-dependent apoptosis are poorly defined. Two-hybrid analyses were used to identify proteins involved in p75NTR apoptotic signaling, and a p75NTR binding partner termed NRAGE (for (n) under bar eurotrophin (r) under bar eceptor-interacting M (A) under bar (G) under bar (E) under bar homolog) was identified. NRAGE binds p75NTR in vitro and in vivo, and NRAGE associates with the plasma membrane when NGF is bound to p75NTR. NRAGE blocks the physical association of p75NTR with TrkA, and, conversely, TrkA overexpression eliminates NRAGE-mediated NGF-dependent death, indicating that interactions of NRAGE or TrkA with p75NTR are functionally and physically exclusive. NRAGE over-expression facilitates cell cycle arrest and permits NGF-dependent apoptosis within sympathetic neuron precursors cells. Our results show that NRAGE contributes to p75NTR-dependent cell death and suggest novel functions for MAGE family proteins.
引用
收藏
页码:279 / 288
页数:10
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