Tong Xiangjun, Xie Dong, Roth Wilfried, Reed John, Koeffler H Phillip
Division of Hematology/Oncology, Cedars-Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA 90048, USA.
Int J Oncol. 2003 Jun;22(6):1357-62.
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.
NADE是一种与p75神经营养因子受体（低亲和力神经营养因子受体p75）相关的细胞死亡执行者，最初是从人卵巢颗粒细胞cDNA文库中克隆出来的，是一种名为pHGR74的未知蛋白质。据报道，它介导神经生长因子诱导的细胞凋亡。我们从乳腺癌细胞系中独立分离出人类NADE（pHGR74）。检测了NADE在各种人类癌细胞系以及人类和小鼠组织中的表达。NADE在人类内分泌相关器官和胚胎小鼠组织中高表达。在CHO（中国仓鼠卵巢）细胞和MDA-MB-231人乳腺癌细胞中强制表达NADE对细胞的体外生长影响不大，而在体内则显著抑制细胞生长。我们利用酵母双杂交系统寻找与NADE结合的蛋白质。动力蛋白被确定为一个候选蛋白。在该实验中未发现p75NTR，且它不与人NADE进行共免疫沉淀。此外，稳定转染NADE的细胞对NGF或TNF无反应。因此，人类和小鼠的NADE似乎具有不同的功能。
