Disease relevance of NGFRAP1

• We independently isolated human NADE (pHGR74) from breast cancer cell lines [1].

High impact information on NGFRAP1

• The designated regulatory region includes the C-terminal amino acid residues (72-112) and is essential for NGF-dependent regulation of NADE-induced apoptosis [2].
• Truncation of a minimal region, including amino acid residues 41-71 of NADE, was found to be sufficient to induce apoptosis [2].
• Furthermore, the mutants with amino acid substitutions in the leucine-rich nuclear export signal (NES) sequence (residues 90-100) abolished the export of NADE from the nucleus to the cytoplasm [2].
• NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR [3].
• NADE plays a role in NGF-induced apoptosis in oligodendrocytes and in zinc-induced neuronal death [4].

Biological context of NGFRAP1

• Direct interaction of Smac with NADE promotes TRAIL-induced apoptosis [5].
• Human Bex gene expression was studied with tissue expression arrays probed with specific oligonucleotides [6].
• We used the yeast two-hybrid system to search for NADE binding protein [1].
• A major site (nt 4534 to 4733) was present only in a cell line of macrophage/monocyte origin in a region of the genome in which an intragenic enhancer was recently identified (E. Verdin, N. Becker, F. Bex, L. Droogmans, and A. Burny, Proc. Natl. Acad. Sci. USA 87:4874-4878, 1990) [7].
• Familial inheritance of PI NADE was demonstrated and both PI M2NADE and PI M3NADE phenotypes were observed [8].

Anatomical context of NGFRAP1

• Human Bex4 is highly expressed in heart, skeletal muscle, and liver, while Bex3 and Bex5 are more widely expressed [6].
• Expression of NADE in various human cancer cell lines, and human and murine tissues was examined [1].
• Surgical procedures included Carpentier ring implant (5 patients), Bex posterior annuloplasty (1 patient), implant of artificial chordae (4 patients), papillary muscle reinsertion (2 patients), commissuroplasty (1 patient) and "artificial double orifice" technique (1 patient) [9].
• The mean freedom rate from tricuspid repair failure (clinical right heart failure, redo annuloplasty, tricuspid valve replacement at follow up) was 95+/-3%, 93+/-3% and 72+/-8% at 5, 10 and 15 years respectively after the De Vega semicircular annuloplasty, and 97+/-1%, 87+/-4% and 66+/-9% after the Bex flexible linear reducer [10].

Associations of NGFRAP1 with chemical compounds

• These findings suggest that DRG-1 may contribute to the dopamine-induced cell growth, which is negatively regulated by NADE [11].
• Recently, a phosphorylation-independent interaction has been reported to occur between 14-3-3 and a small number of proteins, for example the 43 kDa inositol polyphosphate 5-phosphatase, glycoprotein Ib, p75NTR-associated cell-death executor (NADE) and the bacterial ADP-ribosyltransferase toxin exoenzyme S (ExoS) [12].

Other interactions of NGFRAP1

• Furthermore, the cells stably transfected with NADE did not respond to NGF or TNF [1].

References