Regulated commitment of TNF receptor signaling:: A molecular switch for death or activation

被引:241
作者
Pimentel-Muiños, FX [1 ]
Seed, B [1 ]
机构
[1] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA
关键词
D O I
10.1016/S1074-7613(00)80152-1
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:783 / 793
页数:11
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