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| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0035820 | lld:lifeskim |
| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0017710 | lld:lifeskim |
| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0032145 | lld:lifeskim |
| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0034840 | lld:lifeskim |
| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0040690 | lld:lifeskim |
| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0017262 | lld:lifeskim |
| pubmed-article:16423881 | lifeskim:mentions | umls-concept:C0851285 | lld:lifeskim |
| pubmed-article:16423881 | pubmed:issue | 5 | lld:pubmed |
| pubmed-article:16423881 | pubmed:dateCreated | 2006-5-2 | lld:pubmed |
| pubmed-article:16423881 | pubmed:abstractText | TGFbeta is a major regulator of extracellular matrix deposition and a potent inducer of type-1 plasminogen activator inhibitor (PAI-1) gene expression. We have reported that liganded glucocorticoid receptor (GR) represses TGFbeta transactivation of PAI-1 in Hep3B human hepatoma cells and that it interacts functionally and physically with the C-terminal activation domain of Smad3, a mediator of TGFbeta signaling. The ligand binding domain of GR is required for GR-mediated transrepression, but the GR DNA binding domain and activation function 1 domains are not. We report here that overexpression of steroid receptor coactivator-1 (SRC-1) and GR-interacting protein-1 (GRIP-1) enhanced repression by liganded GR, and by a GR mutant defective in repression. Surprisingly, SRC-1 and GRIP-1 also enhanced TGFbeta-induced activation from the TGFbeta-responsive sequence of the PAI-1 gene by a GR-independent mechanism. Coimmunoprecipitation and mammalian one-hybrid experiments demonstrated that SRC-1 and GRIP-1 interact physically with endogenous Smad3 and functionally with the C-terminal domain of Smad3 to directly enhance transcription. Thus, the GR coactivators, SRC-1 and GRIP-1, act as both corepressors of the glucocorticoid repression of PAI-1 gene transcription, and coactivators of TGFbeta-induced activation of the PAI-1 promoter. | lld:pubmed |
| pubmed-article:16423881 | pubmed:language | eng | lld:pubmed |
| pubmed-article:16423881 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:16423881 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:16423881 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:16423881 | pubmed:month | May | lld:pubmed |
| pubmed-article:16423881 | pubmed:issn | 0888-8809 | lld:pubmed |
| pubmed-article:16423881 | pubmed:author | pubmed-author:HeatonJoanne... | lld:pubmed |
| pubmed-article:16423881 | pubmed:author | pubmed-author:GelehrterThom... | lld:pubmed |
| pubmed-article:16423881 | pubmed:author | pubmed-author:LiGangyongG | lld:pubmed |
| pubmed-article:16423881 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:16423881 | pubmed:volume | 20 | lld:pubmed |
| pubmed-article:16423881 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:16423881 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:16423881 | pubmed:pagination | 1025-34 | lld:pubmed |
| pubmed-article:16423881 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:16423881 | pubmed:year | 2006 | lld:pubmed |
| pubmed-article:16423881 | pubmed:articleTitle | Role of steroid receptor coactivators in glucocorticoid and transforming growth factor beta regulation of plasminogen activator inhibitor gene expression. | lld:pubmed |
| pubmed-article:16423881 | pubmed:affiliation | Department of Human Genetics, Box 0618, University of Michigan Medical School, Ann Arbor, Michigan 48109-0618, USA. | lld:pubmed |
| pubmed-article:16423881 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:16423881 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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