{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T07:09:23Z","timestamp":1791616163489,"version":"4.3.4"},"reference-count":35,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2006,3,19]],"date-time":"2006-03-19T00:00:00Z","timestamp":1142726400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2006,3,19]],"date-time":"2006-03-19T00:00:00Z","timestamp":1142726400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Cell Biol"],"published-print":{"date-parts":[[2006,4,1]]},"DOI":"10.1038\/ncb1384","type":"journal-article","created":{"date-parts":[[2006,3,20]],"date-time":"2006-03-20T06:58:28Z","timestamp":1142837908000},"page":"398-406","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":557,"title":["Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-\u03baB activation"],"prefix":"10.1038","volume":"8","author":[{"given":"Chuan-Jin","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich B.","family":"Conze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivasa M.","family":"Srinivasula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Ashwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2006,3,19]]},"reference":[{"key":"BFncb1384_CR1","doi-asserted-by":"publisher","first-page":"2321","DOI":"10.1101\/gad.909001","volume":"15","author":"N Silverman","year":"2001","unstructured":"Silverman, N. & Maniatis, T. NF-\u03baB signaling pathways in mammalian and insect innate immunity. Genes Dev. 15, 2321\u20132342 (2001).","journal-title":"Genes Dev."},{"key":"BFncb1384_CR2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/ni0102-20","volume":"3","author":"Y Ben-Neriah","year":"2002","unstructured":"Ben-Neriah, Y. Regulatory functions of ubiquitination in the immune system. Nature Immunol. 3, 20\u201326 (2002).","journal-title":"Nature Immunol."},{"key":"BFncb1384_CR3","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/S1471-4914(01)02154-2","volume":"7","author":"G Courtois","year":"2001","unstructured":"Courtois, G., Smahi, A. & Israel, A. NEMO\u2013IKK\u03b3: linking NF-\u03baB to human disease. Trends Mol. Med. 7, 427\u2013430 (2001).","journal-title":"Trends Mol. Med."},{"key":"BFncb1384_CR4","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1016\/S1074-7613(00)80535-X","volume":"8","author":"MA Kelliher","year":"1998","unstructured":"Kelliher, M. A. et al. The death domain kinase RIP mediates the TNF-induced NF-\u03baB signal. Immunity 8, 297\u2013303 (1998).","journal-title":"Immunity"},{"key":"BFncb1384_CR5","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S1074-7613(00)80183-1","volume":"12","author":"SQ Zhang","year":"2000","unstructured":"Zhang, S. Q., Kovalenko, A., Cantarella, G. & Wallach, D. Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKK\u03b3) upon receptor stimulation. Immunity 12, 301\u2013311 (2000).","journal-title":"Immunity"},{"key":"BFncb1384_CR6","doi-asserted-by":"publisher","first-page":"655","DOI":"10.1016\/S1074-7613(03)00092-X","volume":"18","author":"DF Legler","year":"2003","unstructured":"Legler, D. F., Micheau, O., Doucey, M. A., Tschopp, J. & Bron, C. Recruitment of TNF receptor 1 to lipid rafts is essential for TNF\u03b1-mediated NF-\u03baB activation. Immunity 18, 655\u2013664 (2003).","journal-title":"Immunity"},{"key":"BFncb1384_CR7","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nature02794","volume":"430","author":"IE Wertz","year":"2004","unstructured":"Wertz, I. E. et al. De-ubiquitination and ubiquitin ligase domains of A20 downregulate NF-\u03baB signalling. Nature 430, 694\u2013699 (2004).","journal-title":"Nature"},{"key":"BFncb1384_CR8","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S0092-8674(00)00126-4","volume":"103","author":"L Deng","year":"2000","unstructured":"Deng, L. et al. Activation of the I\u03baB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103, 351\u2013361 (2000).","journal-title":"Cell"},{"key":"BFncb1384_CR9","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1038\/312663a0","volume":"312","author":"E Ozkaynak","year":"1984","unstructured":"Ozkaynak, E., Finley, D. & Varshavsky, A. The yeast ubiquitin gene: head-to-tail repeats encoding a polyubiquitin precursor protein. Nature 312, 663\u2013666 (1984).","journal-title":"Nature"},{"key":"BFncb1384_CR10","doi-asserted-by":"publisher","first-page":"13425","DOI":"10.1073\/pnas.172511699","volume":"99","author":"SS Hook","year":"2002","unstructured":"Hook, S. S., Orian, A., Cowley, S. M. & Eisenman, R. N. Histone deacetylase 6 binds polyubiquitin through its zinc finger (PAZ domain) and copurifies with deubiquitinating enzymes. Proc. Natl Acad. Sci. USA 99, 13425\u201313430 (2002).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb1384_CR11","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.molcel.2004.08.008","volume":"15","author":"A Kanayama","year":"2004","unstructured":"Kanayama, A. et al. TAB2 and TAB3 activate the NF-\u03baB pathway through binding to polyubiquitin chains. Mol Cell 15, 535\u2013548 (2004).","journal-title":"Mol Cell"},{"key":"BFncb1384_CR12","doi-asserted-by":"publisher","first-page":"27861","DOI":"10.1074\/jbc.M314278200","volume":"279","author":"F Agou","year":"2004","unstructured":"Agou, F. et al. The trimerization domain of NEMO is composed of the interacting C-terminal CC2 and LZ coiled-coil subdomains. J. Biol. Chem. 279, 27861\u201327869 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFncb1384_CR13","doi-asserted-by":"publisher","first-page":"2029","DOI":"10.1128\/MCB.23.6.2029-2041.2003","volume":"23","author":"S Tegethoff","year":"2003","unstructured":"Tegethoff, S., Behlke, J. & Scheidereit, C. Tetrameric oligomerization of I\u03baB kinase\u03b3 (IKK\u03b3) is obligatory for IKK complex activity and NF-\u03baB activation. Mol. Cell Biol. 23, 2029\u20132041 (2003).","journal-title":"Mol. Cell Biol."},{"key":"BFncb1384_CR14","doi-asserted-by":"publisher","first-page":"6573","DOI":"10.1128\/MCB.22.18.6573-6581.2002","volume":"22","author":"C Makris","year":"2002","unstructured":"Makris, C., Roberts, J. L. & Karin, M. The carboxyl-terminal region of I\u03baB kinase\u03b3 (IKK\u03b3) is required for full IKK activation. Mol. Cell Biol. 22, 6573\u20136581 (2002).","journal-title":"Mol. Cell Biol."},{"key":"BFncb1384_CR15","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/85837","volume":"27","author":"R Doffinger","year":"2001","unstructured":"Doffinger, R. et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-\u03baB signaling. Nature Genet. 27, 277\u2013285 (2001).","journal-title":"Nature Genet."},{"key":"BFncb1384_CR16","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1016\/j.cbpa.2004.09.009","volume":"8","author":"CM Pickart","year":"2004","unstructured":"Pickart, C. M. & Fushman, D. Polyubiquitin chains: polymeric protein signals. Curr. Opin. Chem. Biol. 8, 610\u2013616 (2004).","journal-title":"Curr. Opin. Chem. Biol."},{"key":"BFncb1384_CR17","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1042\/bj2520127","volume":"252","author":"GM Trakshel","year":"1988","unstructured":"Trakshel, G. M. & Maines, M. D. Characterization of glutathione S-transferases in rat kidney. Alteration of composition by cis-platinum. Biochem J 252, 127\u2013136 (1988).","journal-title":"Biochem J"},{"key":"BFncb1384_CR18","doi-asserted-by":"publisher","first-page":"33185","DOI":"10.1074\/jbc.M404206200","volume":"279","author":"TH Lee","year":"2004","unstructured":"Lee, T. H., Shank, J., Cusson, N. & Kelliher, M. A. The kinase activity of RIP1 is not required for tumor necrosis factor-\u03b1-induced I\u03baB kinase or p38 MAP kinase activation or for the ubiquitination of RIP1 by TRAF2. J. Biol. Chem. 279, 33185\u201333191 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFncb1384_CR19","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1111\/j.1365-2443.2005.00852.x","volume":"10","author":"S Kishida","year":"2005","unstructured":"Kishida, S., Sanjo, H., Akira, S., Matsumoto, K. & Ninomiya-Tsuji, J. TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway. Genes Cells 10, 447\u2013454 (2005).","journal-title":"Genes Cells"},{"key":"BFncb1384_CR20","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1111\/j.1365-2443.2004.00780.x","volume":"9","author":"T Tenno","year":"2004","unstructured":"Tenno, T. et al. Structural basis for distinct roles of Lys63- and Lys48-linked polyubiquitin chains. Genes Cells 9, 865\u2013875 (2004).","journal-title":"Genes Cells"},{"key":"BFncb1384_CR21","doi-asserted-by":"publisher","first-page":"7055","DOI":"10.1074\/jbc.M309184200","volume":"279","author":"R Varadan","year":"2004","unstructured":"Varadan, R. et al. Solution conformation of Lys63-linked di-ubiquitin chain provides clues to functional diversity of polyubiquitin signaling. J. Biol. Chem. 279, 7055\u20137063 (2004).","journal-title":"J. Biol. Chem."},{"key":"BFncb1384_CR22","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1038\/26261","volume":"395","author":"DM Rothwarf","year":"1998","unstructured":"Rothwarf, D. M., Zandi, E., Natoli, G. & Karin, M. IKK\u03b3 is an essential regulatory subunit of the I\u03baB kinase complex. Nature 395, 297\u2013300 (1998).","journal-title":"Nature"},{"key":"BFncb1384_CR23","doi-asserted-by":"publisher","first-page":"37966","DOI":"10.1074\/jbc.M006643200","volume":"275","author":"JL Poyet","year":"2000","unstructured":"Poyet, J. L. et al. Activation of the I\u03baB kinases by RIP via IKK\u03b3\u2013NEMO-mediated oligomerization. J. Biol. Chem. 275, 37966\u201337977 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFncb1384_CR24","doi-asserted-by":"publisher","first-page":"10519","DOI":"10.1074\/jbc.275.14.10519","volume":"275","author":"J Lewis","year":"2000","unstructured":"Lewis, J. et al. Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-\u03baB activation. J. Biol. Chem. 275, 10519\u201310526 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFncb1384_CR25","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1016\/S1097-2765(02)00450-1","volume":"9","author":"G Chen","year":"2002","unstructured":"Chen, G., Cao, P. & Goeddel, D. V. TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol. Cell 9, 401\u2013410 (2002).","journal-title":"Mol. Cell"},{"key":"BFncb1384_CR26","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1016\/S1471-4906(03)00177-7","volume":"24","author":"M Thome","year":"2003","unstructured":"Thome, M. & Tschopp, J. TCR-induced NF-\u03baB activation: a crucial role for Carma1, Bcl10 and MALT1. Trends Immunol. 24, 419\u2013424 (2003).","journal-title":"Trends Immunol."},{"key":"BFncb1384_CR27","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/nature02273","volume":"427","author":"H Zhou","year":"2004","unstructured":"Zhou, H. et al. Bcl10 activates the NF-\u03baB pathway through ubiquitination of NEMO. Nature 427, 167\u2013171 (2004).","journal-title":"Nature"},{"key":"BFncb1384_CR28","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/nature01802","volume":"424","author":"A Kovalenko","year":"2003","unstructured":"Kovalenko, A. et al. The tumour suppressor CYLD negatively regulates NF-\u03baB signalling by deubiquitination. Nature 424, 801\u2013805 (2003).","journal-title":"Nature"},{"key":"BFncb1384_CR29","doi-asserted-by":"publisher","first-page":"1448","DOI":"10.1038\/sj.onc.1203445","volume":"19","author":"EW Harhaj","year":"2000","unstructured":"Harhaj, E. W. et al. Somatic mutagenesis studies of NF-\u03baB signaling in human T cells: evidence for an essential role of IKK\u03b3 in NF-\u03baB activation by T-cell costimulatory signals and HTLV-I Tax protein. Oncogene 19, 1448\u20131456 (2000).","journal-title":"Oncogene"},{"key":"BFncb1384_CR30","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1016\/S1097-2765(00)80263-4","volume":"5","author":"M Schmidt-Supprian","year":"2000","unstructured":"Schmidt-Supprian, M. et al. NEMO\u2013IKK\u03b3-deficient mice model incontinentia pigmenti. Mol. Cell 5, 981\u2013992 (2000).","journal-title":"Mol. Cell"},{"key":"BFncb1384_CR31","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0076-6879(95)55036-4","volume":"255","author":"AB Vojtek","year":"1995","unstructured":"Vojtek, A. B. & Hollenberg, S. M. Ras\u2013Raf interaction: two-hybrid analysis. Methods Enzymol. 255, 331\u2013342 (1995).","journal-title":"Methods Enzymol."},{"key":"BFncb1384_CR32","doi-asserted-by":"publisher","first-page":"11364","DOI":"10.1073\/pnas.96.20.11364","volume":"96","author":"KL Lorick","year":"1999","unstructured":"Lorick, K. L. et al. RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc. Natl Acad. Sci. USA 96, 11364\u201311369 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncb1384_CR33","doi-asserted-by":"publisher","first-page":"3348","DOI":"10.1128\/MCB.25.8.3348-3356.2005","volume":"25","author":"DB Conze","year":"2005","unstructured":"Conze, D. B. et al. Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo. Mol. Cell Biol. 25, 3348\u20133356 (2005).","journal-title":"Mol. Cell Biol."},{"key":"BFncb1384_CR34","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1101\/gad.10.9.1084","volume":"10","author":"MN Lioubin","year":"1996","unstructured":"Lioubin, M. N. et al. p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity. Genes Dev. 10, 1084\u20131095 (1996).","journal-title":"Genes Dev."},{"key":"BFncb1384_CR35","doi-asserted-by":"publisher","first-page":"15318","DOI":"10.1073\/pnas.0404132101","volume":"101","author":"CK Ea","year":"2004","unstructured":"Ea, C. K., Sun, L., Inoue, J. & Chen, Z. J. TIFA activates I\u03baB kinase (IKK) by promoting oligomerization and ubiquitination of TRAF6. Proc. Natl Acad. Sci. USA 101, 15318\u201315323 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"}],"updated-by":[{"DOI":"10.1038\/ncb1408","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2006,4,16]],"date-time":"2006-04-16T00:00:00Z","timestamp":1145145600000}}],"container-title":["Nature Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ncb1384.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb1384","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb1384.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T15:28:01Z","timestamp":1684423681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncb1384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,3,19]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2006,4,1]]}},"alternative-id":["BFncb1384"],"URL":"https:\/\/doi.org\/10.1038\/ncb1384","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1031705.368827","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1031705.372890","asserted-by":"object"}]},"ISSN":["1465-7392","1476-4679"],"issn-type":[{"value":"1465-7392","type":"print"},{"value":"1476-4679","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,3,19]]},"assertion":[{"value":"21 September 2005","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 February 2006","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2006","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}