Wajant Harald, Pfizenmaier Klaus, Scheurich Peter
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, Germany.
Cytokine Growth Factor Rev. 2003 Feb;14(1):53-66. doi: 10.1016/s1359-6101(02)00072-2.
Fas (Apo-1, CD95) and Fas-Ligand (FasL, CD95L) are typical members of the TNF receptor and TNF ligand family, respectively, with a pivotal role in the regulation of apoptotic processes, including activation-induced cell death, T-cell-induced cytotoxicity, immune privilege and tumor surveillance. Impairment of the FasL/Fas system has been implicated in liver failure, autoimmune diseases and immune deficiency. Thus, the FasL/Fas system was mainly appreciated with respect to its death-inducing capabilities. However, there is increasing evidence that activation of Fas can also result in non-apoptotic responses like cell proliferation or NF-kappaB activation. While the apoptotic features of the FasL/Fas system and the pathways involved are comparably well investigated, the pathways that are utilized by Fas to transduce proliferative and activating signals are poorly understood. This review is focused on the non-apoptotic functions of the FasL/Fas system. In particular, the similarities and differences of the molecular mechanisms of apoptotic and non-apoptotic Fas signaling are addressed.
Fas(Apo-1,CD95)和Fas配体(FasL,CD95L)分别是肿瘤坏死因子受体(TNF受体)家族和肿瘤坏死因子配体家族的典型成员,在凋亡过程的调控中起关键作用,这些凋亡过程包括激活诱导的细胞死亡、T细胞诱导的细胞毒性、免疫赦免和肿瘤监视。FasL/Fas系统功能受损与肝衰竭、自身免疫性疾病及免疫缺陷有关。因此,FasL/Fas系统主要因其诱导细胞死亡的能力而受到关注。然而,越来越多的证据表明,Fas激活也可导致非凋亡反应,如细胞增殖或核因子κB(NF-κB)激活。虽然FasL/Fas系统的凋亡特征及相关途径已得到较为充分的研究,但Fas用于转导增殖和激活信号的途径却知之甚少。本综述聚焦于FasL/Fas系统的非凋亡功能。特别探讨了凋亡和非凋亡Fas信号传导分子机制的异同。