Regulated commitment of TNF receptor signaling:: A molecular switch for death or activation
Regulated commitment of TNF receptor signaling:: A molecular switch for death or activation
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DOI：
10.1016/s1074-7613(00)80152-1
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发表时间：
1999-12-01
期刊：
影响因子：
32.4
通讯作者：
Seed, B
中科院分区：
文献类型：
--
作者：
Pimentel-Muiños, FX;Seed, B
肿瘤坏死因子受体（TNFR）超家族成员可以诱导环境依赖性细胞凋亡或细胞活化。然而，选择这些相反方案的机制仍不清楚。我们发现，在T细胞中，TNFR2 （TNFRSF1B）信号传导受到细胞内介质RIP的显著影响，RIP是TNFR1 （TNFRSF1A）激活NF-kappa B所需的一种丝氨酸/苏氨酸蛋白激酶。在RIP存在时，TNFRP触发细胞死亡，而在RIP不存在时，TNFR2激活NF-kappa b。RIP在il - 2驱动的T细胞增殖过程中被诱导，其抑制作用降低了对tnf依赖性细胞凋亡的易感性。信号输出受细胞内约束的证据有助于调和TNFR1和TNFRP作为凋亡介质的相互矛盾的观点。
Tumor necrosis factor receptor (TNFR) superfamily members can induce a context-dependent apoptosis or cell activation. However, the mechanisms by which these opposing programs are selected remain unclear. We show that in T cells, TNFR2 (TNFRSF1B) signaling is dramatically affected by the intracellular mediator RIP, a protein Ser/Thr kinase required for NF-kappa B activation by TNFR1 (TNFRSF1A). In the presence of RIP, TNFRP triggers cell death, whereas in the absence of RIP, TNFR2 activates NF-kappa B. RIP is induced during IL2-driven T cell proliferation, and its inhibition reduces susceptibility to TNF-dependent apoptosis. Evidence that signaling outputs are shaped by intracellular constraints helps reconcile conflicting views of TNFR1 and TNFRP as apoptotic mediators.