The many roles of FAS receptor signaling in the immune system.
The many roles of FAS receptor signaling in the immune system.
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DOI：
10.1016/j.immuni.2009.01.001
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发表时间：
2009-02-20
期刊：
影响因子：
32.4
通讯作者：
Nagata, Shigekazu
中科院分区：
文献类型：
--
作者：
Strasser, Andreas;Jost, Philipp J.;Nagata, Shigekazu
FAS（也称为APO-1或CD 95）属于肿瘤坏死因子受体（TNF-R）家族的亚组，该家族含有细胞内的“死亡结构域”并可触发细胞凋亡。其生理配体FASL（CD 95 L）是相应的TNF细胞因子家族的成员。对自发突变小鼠、基因靶向小鼠和人类患者细胞的研究表明，FAS和FASL在免疫系统中发挥关键作用，特别是在杀死病原体感染的靶细胞和杀死不再需要的、潜在有害的以及自身反应性淋巴细胞方面。因此，这种配体-受体对充当针对自身免疫和肿瘤发展的监护人。FASL-FAS信号转导通过FADD（具有死亡结构域的Fas相关蛋白，也称为MORT 1）衔接蛋白介导的招募和激活腺苷酸特异性半胱氨酸蛋白酶caspase-8触发细胞凋亡。在某些细胞如肝细胞中，尽管不是在淋巴细胞中，但FAS诱导的凋亡信号传导需要通过促凋亡BCL-2家族成员BID的蛋白水解活化来扩增。令人好奇的是，FAS信号机制的几种组分涉及非凋亡过程，包括细胞活化，分化和增殖。在这里，我们描述了目前的知识FASL和FAS在免疫系统中的作用，讨论重要的未解决的问题，并提出实验方法来解决这些问题。
FAS (also known as APO-1 or CD95) belongs to the subgroup of the tumor necrosis factor receptor (TNF-R) family that contain an intra-cellular ‘death domain’ and can trigger apoptosis. Its physiological ligand, FASL (CD95L), is a member of the corresponding TNF cytokine family. Studies with spontaneous mutant mice, gene-targeted mice and cells from human patients have shown that FAS and FASL play critical roles in the immune system, in particular in the killing of pathogen infected target cells and the death of no longer needed, potentially deleterious as well as autoreactive lymphocytes. This ligand-receptor pair thereby functions as a guardian against autoimmunity and tumor development. FASL-FAS signaling triggers apoptosis through FADD (Fas-associated protein with death domain, also called MORT1) adaptor protein-mediated recruitment and activation of the aspartate-specific cysteine protease, caspase-8. In certain cells such as hepatocytes, albeit not in lymphocytes, FAS-induced apoptosis signaling requires amplification through proteolytic activation of the pro-apoptotic BCL-2 family member BID. Curiously, several components of the FAS signaling machinery have been implicated in non-apoptotic processes, including cellular activation, differentiation and proliferation. Here we describe current knowledge of the roles of FASL and FAS in the immune system, discuss important unresolved issues and propose experimental approaches to address them.
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影响因子：
4.4
作者：
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