Speiser D E, Lee S Y, Wong B, Arron J, Santana A, Kong Y Y, Ohashi P S, Choi Y
Ontario Cancer Institute, Departments of Medical Biophysics and Immunology, Toronto, Ontario M5G 2M9, Canada.
J Exp Med. 1997 May 19;185(10):1777-83. doi: 10.1084/jem.185.10.1777.
Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) and TRAF1 were found as components of the TNFR2 signaling complex, which exerts multiple biological effects on cells such as cell proliferation, cytokine production, and cell death. In the TNFR2-mediated signaling pathways, TRAF2 works as a mediator for activation signals such as NF-kappaB, but the role of TRAF1 has not been previously determined. Here we show in transgenic mice that TRAF1 overexpression inhibits antigen-induced apoptosis of CD8(+) T lymphocytes. Our results demonstrate a biological role for TRAF1 as a regulator of apoptotic signals and also support the hypothesis that the combination of TRAF proteins in a given cell type determines distinct biological effects triggered by members of the TNF receptor superfamily.
肿瘤坏死因子受体(TNFR)相关因子2(TRAF2)和TRAF1被发现是TNFR2信号复合物的组成成分,该复合物对细胞发挥多种生物学效应,如细胞增殖、细胞因子产生和细胞死亡。在TNFR2介导的信号通路中,TRAF2作为激活信号(如核因子κB)的介质发挥作用,但TRAF1的作用此前尚未明确。在此,我们在转基因小鼠中发现,TRAF1的过表达抑制抗原诱导的CD8(+) T淋巴细胞凋亡。我们的结果证明了TRAF1作为凋亡信号调节因子的生物学作用,也支持了这样一种假说,即特定细胞类型中TRAF蛋白的组合决定了肿瘤坏死因子受体超家族成员触发的不同生物学效应。