| pubmed-article:12223098 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C1334290 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C1334291 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0225369 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0009331 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C1413580 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C1333079 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0086860 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0444669 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C1521840 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C1514873 | lld:lifeskim |
| pubmed-article:12223098 | lifeskim:mentions | umls-concept:C0379862 | lld:lifeskim |
| pubmed-article:12223098 | pubmed:issue | Pt 1 | lld:pubmed |
| pubmed-article:12223098 | pubmed:dateCreated | 2002-12-11 | lld:pubmed |
| pubmed-article:12223098 | pubmed:abstractText | Interferon-gamma (IFN-gamma) inhibits the synthesis of the cartilage-specific extracellular matrix protein type II collagen, and suppresses the expression of the type II collagen gene ( COL2A1 ) at the transcriptional level. To further examine this mechanism, the responses of COL2A1 regulatory sequences to IFN-gamma and the role of components of the Janus kinase/signal transducer and activators of transcription (JAK/STAT) pathway were examined in the immortalized human chondrocyte cell line, C-28/I2. IFN-gamma inhibited the mRNA levels of COL2A1 and aggrecan, but not Sox9, L-Sox5 and Sox6, all of which were expressed by these cells as markers of the differentiated phenotype. IFN-gamma suppressed the expression of luciferase reporter constructs containing sequences of the COL2A1 promoter spanning -6368 to +125 bp in the absence and presence of the intronic enhancer and stimulated activity of the gamma-interferon-activated site (GAS) luciferase reporter vector, associated with induction of Stat1 alpha-binding activity in nuclear extracts. These responses to IFN-gamma were blocked by overexpression of the JAK inhibitor, JAK-binding protein (JAB), or reversed by dominant-negative Stat1 alpha Y701F containing a mutation at Tyr-701, the JAK phosphorylation site. IFN-gamma had no effect on COL2A1 promoter expression in Jak1 (U4A)-, Jak2 (gamma 2A)- and Stat1 alpha (U3A)-deficient cell lines. In the U3A cell line, the response to IFN-gamma was rescued by overexpression of Stat1 alpha, but not by either Stat1 alpha Y701F or Stat1 beta. Functional analysis using deletion constructs showed that the IFN-gamma response was retained in the COL2A1 core promoter region spanning -45 to +11 bp, containing the TATA-box and GC-rich sequences but no Stat1-binding elements. Inhibition of COL2A1 promoter activity by IFN-gamma persisted in the presence of multiple deletions within the -45/+11 bp region. Our results indicate that repression of COL2A1 gene transcription by IFN-gamma requires Jak1, Jak2 and Stat1 alpha and suggest that this response involves indirect interaction of activated Stat1 alpha with the general transcriptional machinery that drives constitutive COL2A1 expression. | lld:pubmed |
| pubmed-article:12223098 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12223098 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12223098 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12223098 | pubmed:month | Jan | lld:pubmed |
| pubmed-article:12223098 | pubmed:issn | 0264-6021 | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:AuronPhilip... | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:OsakiMakotoM | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:YoshidaYasuhi... | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:TanLujianL | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:GoldringMary... | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:CheahKathryn... | lld:pubmed |
| pubmed-article:12223098 | pubmed:author | pubmed-author:ChoyBob KBK | lld:pubmed |
| pubmed-article:12223098 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12223098 | pubmed:day | 1 | lld:pubmed |
| pubmed-article:12223098 | pubmed:volume | 369 | lld:pubmed |
| pubmed-article:12223098 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12223098 | pubmed:authorsComplete | Y | lld:pubmed |
