NADE (p75NTR-associated cell death executor) suppresses cellular growth in vivo.
NADE, a p75NTR (low-affinity neurotrophin receptor p75) -associated cell death executor, was initially cloned from a human ovarian granulosa cell cDNA library, as an unknown protein with the name, pHGR74. It was reported to mediate nerve growth factor-induced apoptosis. We independently isolated human NADE (pHGR74) from breast cancer cell lines. Expression of NADE in various human cancer cell lines, and human and murine tissues was examined. NADE was highly expressed in human endocrine-related organs and embryotic murine tissues. Forced expression of NADE in CHO (Chinese hamster ovary) cells and MDA-MB-231 human breast cancer cells had little effect on the growth of the cells in vitro, while it dramatically suppressed cellular growth in vivo. We used the yeast two-hybrid system to search for NADE binding protein. Dynactin was identified as a candidate. The p75NTR was not found in this assay and did not co-immunoprecipitate with human NADE. Furthermore, the cells stably transfected with NADE did not respond to NGF or TNF. Thus, human and murine NADE appear to have different functions.
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Xiangjun
X
Tong
Dong
D
Xie
Wilfried
W
Roth
John
J
Reed
H Phillip
HP
Koeffler
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D015723:Gene Library; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000494:pharmacology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D009414:Nerve Growth Factors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha