Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappa B activation prevents cell death
Dissection of TNF receptor 1 effector functions: JNK activation is not linked to apoptosis while NF-kappa B activation prevents cell death
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DOI：
10.1016/s0092-8674(00)81375-6
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发表时间：
1996-11-01
期刊：
影响因子：
64.5
通讯作者：
Karin, M
中科院分区：
文献类型：
--
作者：
Liu, ZG;Hsu, HL;Karin, M
细胞因子肿瘤坏死因子通过其1型受体(TNFR1)引起一系列异常广泛的生物学反应，包括炎症、肿瘤坏死、细胞增殖、分化和凋亡。我们研究了TNFR1如何激活不同的效应器功能：蛋白激酶JNK、转录因子NF-kappa B和细胞凋亡。我们发现，这三种反应是通过不同的途径进行调节的。信号转导分子FADD到TNFR1复合体的募集介导了细胞凋亡，而不是核因子-kappaB或JNK的激活。另外两个信号转导分子RIP和TRAF2同时调节JNK和核因子-kappaB的激活。然而，这两种反应在下游分流到TRAF2。最重要的是，JNK的激活不参与细胞凋亡的诱导，而核因子-kappaB的激活对肿瘤坏死因子诱导的细胞凋亡具有保护作用。
Through its type 1 receptor (TNFR1), the cytokine TNF elicits an unusually wide range of biological responses, including inflammation, tumor necrosis, cell proliferation, differentiation, and apoptosis. We investigated how TNFR1 activates different effector functions; the protein kinase JNK, transcription factor NF-kappa B, and apoptosis. We found that the three responses are mediated through separate pathways. Recruitment of the signal transducer FADD to the TNFR1 complex mediates apoptosis but not NF-kappa B or JNK activation. Two other signal transducers, RIP and TRAF2, mediate both JNK and NF-kappa B activation. These two responses, however, diverge downstream to TRAF2. Most importantly, JNK activation is not involved in induction of apoptosis, while activation of NF-kappa B protects against TNF-induced apoptosis.