Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation
Recruitment of TNF receptor 1 to lipid rafts is essential for TNFα-mediated NF-κB activation
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DOI：
10.1016/s1074-7613(03)00092-x
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发表时间：
2003-05-01
期刊：
影响因子：
32.4
通讯作者：
Bron, C
中科院分区：
文献类型：
--
作者：
Legler, DF;Micheau, O;Bron, C
TNF α与TNF受体1的结合可激活转录因子NF-κ B，但也可诱导细胞凋亡。在这里，我们表明，TNF α结合后，TNFR 1易位到胆固醇和鞘脂富集的膜微区，称为脂筏，在那里它与丝氨酸/苏氨酸激酶RIP和衔接蛋白TRADD和TRAF 2，形成一个信号复合物。在脂筏中，TNFR 1和RIP被泛素化。此外，我们提供的证据表明，转运到脂筏之前泛素化，这导致通过蛋白酶体途径的降解。干扰脂筏组织不仅可以消除泛素化，还可以将TNF α信号从NF-κ B激活转换为凋亡。我们认为，脂筏是至关重要的TNFa激活的信号通路的结果。
Engagement of TNF receptor 1 by TNFalpha activates the transcription factor NF-kappaB but can also induce apoptosis. Here we show that upon TNFalpha binding, TNFR1 translocates to cholesterol- and sphingolipid-enriched membrane microdomains, termed lipid rafts, where it associates with the Ser/Thr kinase RIP and the adaptor proteins TRADD and TRAF2, forming a signaling complex. In lipid rafts, TNFR1 and RIP are ubiquitylated. Furthermore, we provide evidence that translocation to lipid rafts precedes ubiquitylation, which leads to the degradation via the proteasome pathway. Interfering with lipid raft organization not only abolishes ubiquitylation but switches TNFalpha signaling from NF-kappaB activation to apoptosis. We suggest that lipid rafts are crucial for the outcome of TNFalpha-activated signaling pathways.