Tumor necrosis factor receptor mediates fibroblast growth factor-inducible 14 signaling
Tumor necrosis factor receptor mediates fibroblast growth factor-inducible 14 signaling
复制标题
肿瘤坏死因子受体介导成纤维细胞生长因子诱导的 14 信号传导
DOI：
10.1159/000480530
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发表时间：
2017
影响因子：
--
通讯作者：
Yumin xia
中科院分区：
文献类型：
--
作者：
Xuening Wang;Shengxiang Xiao;Yumin xia
肿瘤坏死因子相关的弱凋亡诱导因子(TWEK)与其唯一受体成纤维细胞生长因子诱导的14(Fn14)结合，参与多种炎症和免疫过程。TWAKE/Fn14相互作用根据局部微环境诱导不同的细胞命运，这与肿瘤坏死因子受体(TNFR)的某些表达谱有关。在TWEEP/Fn14激活过程中，TNFR1和TNFR2的优势表达分别促进细胞死亡和增殖。TNFR相关因子(TRAF)与Fn14、细胞凋亡抑制蛋白(CIAP)-1和TNFR相互作用，从而将信号从TWINE传递到下游的细胞因子和细胞周期调节因子。Fn14-TRAF2-TNFR轴在TWEEP/Fn14信号转导中的作用已被提出，这可能成为许多疾病的新治疗策略的靶点，这些疾病的病变组织中有Fn14过表达的细胞。本文的目的是：1)介绍TWEE/Fn14对细胞命运调控的主要结果，2)分析Fn14-TRAF2-TNFR轴的机制，3)总结该轴的药物靶向的潜在策略。
Tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) engages its sole receptor, fibroblast growth factor–inducible 14 (Fn14), which participates in various inflammatory and immunologic processes. TWEAK/Fn14 interaction induces different cell fates depending on the local microenvironment, which correlates with certain expression profiles of TNF receptors (TNFR). The predominant expression of TNFR1 or TNFR2 facilitates cell death or proliferation, respectively, on TWEAK/Fn14 activation. TNFR-associated factors (TRAF) interact with Fn14, cellular inhibitor of apoptosis protein (cIAP)-1, and TNFR, consequently transducing signals from TWEAK to downstream cytokines and cell cycle mediators. An Fn14-TRAF2-TNFR axis has been suggested in the function of TWEAK/Fn14 signaling, which may serve as a target in the development of novel therapeutic strategies for many diseases that have Fn14-overexpressing cells in affected tissues. The aims of this review are: 1) to present the main results on TWEAK/Fn14 regulation of cell fates, 2) to analyze the mechanism of the Fn14-TRAF2-TNFR axis, and 3) to summarize the potential strategies in the pharmacologic targeting of this axis.