14-3-3 is involved in p75 neurotrophin receptor-mediated signal transduction

The low affinity neurotrophin receptor (p75NTR) has been shown to mediate t he apoptosis signaling to neural cells. However, the specific mechanisms of intracellular signal transduction of this process are largely unknown, To understand p75NTR-mediated signal transduction, we previously identified a protein that interacts with the intracellular domain of p75NTR, and we name d it p75NTR-associated cell death executor (NADE), To elucidate further the signaling mechanisms utilized by p75NTR and NADE, we screened for NADE-bin ding protein(s) with the yeast two-hybrid method, and we identified 14-3-3 is an element of as a NADE-binding protein in vivo. To examine whether 14-3 -3 is an element of affects the induction of p75NTR-mediated apoptosis, wil d type or various deletion mutant forms of 14-3-3 were co-expressed in HEK2 93, PC12nnr5, and oligodendrocytes. Interestingly, transient expression of the mutant form of 14-3-3 is an element of lacking the 208-255 amino acid r egion blocked nerve growth factor-dependent p75NTR/NADE-mediated apoptosis, although this mutant form of 14-3-3 is an element of continued to associat e with NADE, These results suggest that 14-3-3 is an element of plays an im portant role in the modulation of nerve growth factor-dependent p75NTR/NADE -mediated apoptosis.