| http://purl.uniprot.org/citations/17562858 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17562858 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17562858 | http://www.w3.org/2000/01/rdf-schema#comment | "K63 polyubiquitin chains spatially and temporally link innate immune signaling effectors such that cytokine release can be coordinated. Crohn's disease is a prototypical inflammatory disorder in which this process may be faulty as the major Crohn's disease-associated protein, NOD2 (nucleotide oligomerization domain 2), regulates the formation of K63-linked polyubiquitin chains on the I kappa kinase (IKK) scaffolding protein, NEMO (NF-kappaB essential modifier). In this work, we study these K63-linked ubiquitin networks to begin to understand the biochemical basis for the signaling cross talk between extracellular pathogen Toll-like receptors (TLRs) and intracellular pathogen NOD receptors. This work shows that TLR signaling requires the same ubiquitination event on NEMO to properly signal through NF-kappaB. This ubiquitination is partially accomplished through the E3 ubiquitin ligase TRAF6. TRAF6 is activated by NOD2, and this activation is lost with a major Crohn's disease-associated NOD2 allele, L1007insC. We further show that TRAF6 and NOD2/RIP2 share the same biochemical machinery (transforming growth factor beta-activated kinase 1 [TAK1]/TAB/Ubc13) to activate NF-kappaB, allowing TLR signaling and NOD2 signaling to synergistically augment cytokine release. These findings suggest a biochemical mechanism for the faulty cytokine balance seen in Crohn's disease."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.00270-07"xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.org/dc/terms/identifier | "doi:10.1128/mcb.00270-07"xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Cantley L.C."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Cantley L.C."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Yang Y."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Abbott D.W."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Abbott D.W."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Kelliher M.A."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Kelliher M.A."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Madhavarapu S."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Madhavarapu S."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Hutti J.E."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/author | "Hutti J.E."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/name | "Mol. Cell. Biol."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/name | "Mol. Cell. Biol."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/pages | "6012-6025"xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/pages | "6012-6025"xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/title | "Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains."xsd:string |
| http://purl.uniprot.org/citations/17562858 | http://purl.uniprot.org/core/title | "Coordinated regulation of Toll-like receptor and NOD2 signaling by K63-linked polyubiquitin chains."xsd:string |