| http://purl.uniprot.org/citations/24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24591377 | http://www.w3.org/2000/01/rdf-schema#comment | "The transcription factor NF-κB is a regulator of inflammatory and adaptive immune responses, yet only IκBα was shown to limit NF-κB activation and inflammatory responses. We investigated another negative feedback regulator, IκBε, in the regulation of B cell proliferation and survival. Loss of IκBε resulted in increased B cell proliferation and survival in response to both antigenic and innate stimulation. NF-κB activity was elevated during late-phase activation, but the dimer composition was stimulus specific. In response to IgM, cRel dimers were elevated in IκBε-deficient cells, yet in response to LPS, RelA dimers also were elevated. The corresponding dimer-specific sequences were found in the promoters of hyperactivated genes. Using a mathematical model of the NF-κB-signaling system in B cells, we demonstrated that kinetic considerations of IκB kinase-signaling input and IκBε's interactions with RelA- and cRel-specific dimers could account for this stimulus specificity. cRel is known to be the key regulator of B cell expansion. We found that the RelA-specific phenotype in LPS-stimulated cells was physiologically relevant: unbiased transcriptome profiling revealed that the inflammatory cytokine IL-6 was hyperactivated in IκBε(-/-) B cells. When IL-6R was blocked, LPS-responsive IκBε(-/-) B cell proliferation was reduced to near wild-type levels. Our results provide novel evidence for a critical role for immune-response functions of IκBε in B cells; it regulates proliferative capacity via at least two mechanisms involving cRel- and RelA-containing NF-κB dimers. This study illustrates the importance of kinetic considerations in understanding the functional specificity of negative-feedback regulators."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1302351"xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Shokhirev M.N."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Hoffmann A."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Fujimoto J."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Alves B.N."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Almaden J."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Tsui R."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Davis-Turak J."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Ponomarenko J."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/author | "Birnbaum H."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/pages | "3121-3132"xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/title | "IkappaBepsilon is a key regulator of B cell expansion by providing negative feedback on cRel and RelA in a stimulus-specific manner."xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://purl.uniprot.org/core/volume | "192"xsd:string |
| http://purl.uniprot.org/citations/24591377 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24591377 |
| http://purl.uniprot.org/citations/24591377 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24591377 |
| http://purl.uniprot.org/uniprot/#_E0CY50-mappedCitation-24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24591377 |
| http://purl.uniprot.org/uniprot/#_P15307-mappedCitation-24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24591377 |
| http://purl.uniprot.org/uniprot/#_A4L9Q2-mappedCitation-24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24591377 |
| http://purl.uniprot.org/uniprot/#_A0A3B2WAY2-mappedCitation-24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24591377 |
| http://purl.uniprot.org/uniprot/#_A0A494B901-mappedCitation-24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24591377 |
| http://purl.uniprot.org/uniprot/#_A0A494BA44-mappedCitation-24591377 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24591377 |