Mostrar el registro sencillo del ítem
dc.contributor.author
Alvarez, Sergio Eduardo
dc.contributor.author
Harikumar, Kuzhuvelil B.
dc.contributor.author
Hait, Nitai C.
dc.contributor.author
Allegood, Jeremy
dc.contributor.author
Strub, Graham M.
dc.contributor.author
Kim, Eugene Y.
dc.contributor.author
Maceycka, Michael
dc.contributor.author
Jiang, Hualiang
dc.contributor.author
Lu, Cheng
dc.contributor.author
Kordula, Tomasz
dc.contributor.author
Milstien, Sheldon
dc.contributor.author
Spiegel, Sarah
dc.date.available
2017-03-31T18:00:41Z
dc.date.issued
2010-06
dc.identifier.citation
Alvarez, Sergio Eduardo; Harikumar, Kuzhuvelil B.; Hait, Nitai C.; Allegood, Jeremy; Strub, Graham M.; et al.; Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2; Nature Publishing Group; Nature; 465; 7301; 6-2010; 1084-1088
dc.identifier.issn
0028-0836
dc.identifier.uri
http://hdl.handle.net/11336/14601
dc.description.abstract
Tumour-necrosis factor (TNF) receptor-associated factor 2 (TRAF2) is a key component in NF-κB signalling triggered by TNF-α1, 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 IκB kinase, leading to activation of the transcription factor NF-κB. 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 IκB kinase and IκBα, and IκBα degradation, leading to NF-κB 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-α signalling and the canonical NF-κB activation pathway important in inflammatory, antiapoptotic and immune processes.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Nature Publishing Group
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Nf-Kb
dc.subject
Sphingosine-1-Phosphate
dc.subject
Ubiquitination
dc.subject
Sphingosine Kinase
dc.subject.classification
Biología Celular, Microbiología
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Sphingosine-1-phosphate is a missing cofactor for the E3 ubiquitin ligase TRAF2
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-03-30T17:43:06Z
dc.identifier.eissn
1476-4687
dc.journal.volume
465
dc.journal.number
7301
dc.journal.pagination
1084-1088
dc.journal.pais
Reino Unido
dc.journal.ciudad
Londres
dc.description.fil
Fil: Alvarez, Sergio Eduardo. Virginia Commonwealth University. School of Medicine; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
dc.description.fil
Fil: Harikumar, Kuzhuvelil B.. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Hait, Nitai C.. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Allegood, Jeremy. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Strub, Graham M.. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Kim, Eugene Y.. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Maceycka, Michael. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Jiang, Hualiang. Chinese Academy of Sciences. Shangai Institute of Materia Medica. State Key Laboratory of Drug Research; China
dc.description.fil
Fil: Lu, Cheng. Chinese Academy of Sciences. Shangai Institute of Materia Medica. State Key Laboratory of Drug Research; China
dc.description.fil
Fil: Kordula, Tomasz. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Milstien, Sheldon. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.description.fil
Fil: Spiegel, Sarah. Virginia Commonwealth University. School of Medicine; Estados Unidos
dc.journal.title
Nature
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.nature.com/nature/journal/v465/n7301/full/nature09128.html
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1038/nature09128
Archivos asociados