| http://purl.uniprot.org/citations/23740952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23740952 | http://www.w3.org/2000/01/rdf-schema#comment | "The CXCL10 gene encodes a peptide that chemoattracts a variety of leukocytes associated with type 1 and type 2 diabetes. The present study was undertaken to determine the molecular mechanisms required for expression of the CXCL10 gene in response to IL-1β and IFN-γ using rat islets and β cell lines. IL-1β induced the expression of the CXCL10 gene and promoter activity, whereas the combination of IL-1β plus IFN-γ was synergistic. Small interfering RNA-mediated suppression of NF-κB p65 markedly inhibited the ability of cytokines to induce the expression of the CXCL10 gene, whereas targeting STAT1 only diminished the synergy provided by IFN-γ. Furthermore, we found that a JAK1 inhibitor dose dependently reduced IFN-γ-controlled CXCL10 gene expression and promoter activity, concomitant with a decrease in STAT1 phosphorylation at Tyr(701). We further discovered that, although the Tyr(701) phosphorylation site is inducible (within 15 min of IFN-γ exposure), the Ser(727) site within STAT1 is constitutively phosphorylated. Thus, we generated single-mutant STAT1 Y701F and double-mutant STAT1 Y701F/S727A adenoviruses. Using these recombinant adenoviruses, we determined that overexpression of either the single- or double-mutant STAT1 decreased the IFN-γ-mediated potentiation of CXCL10 gene expression, promoter activity, and secretion of protein. Moreover, the Ser(727) phosphorylation was neither contingent on a functional Y701 site in β cells nor was it required for cytokine-mediated expression of the CXCL10 gene. We conclude that the synergism of IL-1β and IFN-γ to induce expression of the CXCL10 gene requires NF-κB, STAT1 phosphorylated at Tyr(701), recruitment of coactivators, and acetylation of histones H3 and H4."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.org/dc/terms/identifier | "doi:10.4049/jimmunol.1300344"xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/author | "Lu D."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/author | "Proud D."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/author | "Collier J.J."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/author | "Burke S.J."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/author | "Goff M.R."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/author | "Karlstad M.D."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/date | "2013"xsd:gYear |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/name | "J Immunol"xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/pages | "323-336"xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/title | "Synergistic expression of the CXCL10 gene in response to IL-1beta and IFN-gamma involves NF-kappaB, phosphorylation of STAT1 at Tyr701, and acetylation of histones H3 and H4."xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://purl.uniprot.org/core/volume | "191"xsd:string |
| http://purl.uniprot.org/citations/23740952 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/23740952 |
| http://purl.uniprot.org/citations/23740952 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/23740952 |
| http://purl.uniprot.org/uniprot/#_A0A7R8GUN6-mappedCitation-23740952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23740952 |
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| http://purl.uniprot.org/uniprot/#_A0A510GDC6-mappedCitation-23740952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23740952 |
| http://purl.uniprot.org/uniprot/#_A5D905-mappedCitation-23740952 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/23740952 |
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