Recruitment of TNF Receptor 1 to Lipid Rafts Is Essential for TNFα-Mediated NF-κB Activation

Engagement of TNF receptor 1 by TNFα activates the transcription factor NF-κB but can also induce apoptosis. Here we show that upon TNFα binding, TNFR1 translocates to cholesterol- and sphingolipid-enriched membrane microdomains, termed lipid rafts, where it associates with the Ser/Thr kinase RIP an...

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Published inImmunity (Cambridge, Mass.) Vol. 18; no. 5; pp. 655 - 664
Main Authors Legler, Daniel F, Micheau, Olivier, Doucey, Marie-Agnès, Tschopp, Jürg, Bron, Claude
Format Journal Article
LanguageEnglish
Published Elsevier Inc 01.05.2003
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Summary:Engagement of TNF receptor 1 by TNFα activates the transcription factor NF-κB but can also induce apoptosis. Here we show that upon TNFα 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 TNFα signaling from NF-κB activation to apoptosis. We suggest that lipid rafts are crucial for the outcome of TNFα-activated signaling pathways.
Bibliography:ObjectType-Article-2
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ISSN:1074-7613
1097-4180
DOI:10.1016/S1074-7613(03)00092-X