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Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2
文献类型：期刊论文
| 作者 | Alvarez, Sergio E.1,2; Harikumar, Kuzhuvelil B.1,2; Hait, Nitai C.1,2; Allegood, Jeremy1,2; Strub, Graham M.1,2; Kim, Eugene Y.1,2; Maceyka, Michael1,2; Jiang, Hualiang3 ; Luo, Cheng3; Kordula, Tomasz1,2
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| 刊名 | NATURE
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| 出版日期 | 2010-06-24 |
| 卷号 | 465期号:7301页码:1084-U149 |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature09128 |
| 文献子类 | Article |
| 英文摘要 | Tumour-necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a key component in NF-kappa B signalling triggered by TNF-alpha(1,2). Genetic evidence indicates that TRAF2 is necessary for the polyubiquitination of receptor interacting protein 1 (RIP1)(3) that then serves as a platform for recruitment and stimulation of I kappa B kinase, leading to activation of the transcription factor NF-kappa B. Although TRAF2 is a RING domain ubiquitin ligase, direct evidence that TRAF2 catalyses the ubiquitination of RIP1 is lacking. TRAF2 binds to sphingosine kinase 1 (SphK1)(4), one of the isoenzymes that generates the pro-survival lipid mediator sphingosine-1-phosphate (S1P) inside cells. Here we show that SphK1 and the production of S1P is necessary for lysine-63-linked polyubiquitination of RIP1, phosphorylation of I kappa B kinase and I kappa B alpha, and I kappa B alpha degradation, leading to NF-kappa B activation. These responses were mediated by intracellular S1P independently of its cell surface G-protein-coupled receptors. S1P specifically binds to TRAF2 at the amino-terminal RING domain and stimulates its E3 ligase activity. S1P, but not dihydro-S1P, markedly increased recombinant TRAF2-catalysed lysine-63-linked, but not lysine-48-linked, polyubiquitination of RIP1 in vitro in the presence of the ubiquitin conjugating enzymes (E2) UbcH13 or UbcH5a. Our data show that TRAF2 is a novel intracellular target of S1P, and that S1P is the missing cofactor for TRAF2 E3 ubiquitin ligase activity, indicating a new paradigm for the regulation of lysine-63-linked polyubiquitination. These results also highlight the key role of SphK1 and its product S1P in TNF-alpha signalling and the canonical NF-kappa B activation pathway important in inflammatory, antiapoptotic and immune processes. |
| WOS关键词 | NF-KAPPA-B ; SPHINGOSINE 1-PHOSPHATE ; ENDOTHELIAL-CELLS ; TNF-ALPHA ; ACTIVATION ; POLYUBIQUITIN ; KINASE-1 ; RIP1 ; IKK ; PHOSPHORYLATION |
| 资助项目 | National Institute of Health[R37GM043880] ; National Institute of Health[R01CA61774] ; National Institute of Health[R01AI50094] ; National Institute of Health[U19AI077435] ; Ministry of Scientific and Technology of China[2009CB918502] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000279056900054 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278868]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Spiegel, Sarah |
| 作者单位 | 1.Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Sch Med, Richmond, VA 23298 USA; 2.Virginia Commonwealth Univ, Massey Canc Ctr, Sch Med, Richmond, VA 23298 USA; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Alvarez, Sergio E.,Harikumar, Kuzhuvelil B.,Hait, Nitai C.,et al. Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2[J]. NATURE,2010,465(7301):1084-U149. |
| APA | Alvarez, Sergio E..,Harikumar, Kuzhuvelil B..,Hait, Nitai C..,Allegood, Jeremy.,Strub, Graham M..,...&Spiegel, Sarah.(2010).Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2.NATURE,465(7301),1084-U149. |
| MLA | Alvarez, Sergio E.,et al."Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2".NATURE 465.7301(2010):1084-U149. |
入库方式： OAI收割
来源：上海药物研究所
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