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| Content Provider | PubMed Central |
|---|---|
| Author | Pascual, Gabriel Fong, Amy L. Ogawa, Sumito Gamliel, Amir Li, Andrew C. Valentina, Perissi Rose, David W. Willson, Timothy Rosenfeld, Michael G. Glass, Christopher K. |
| Abstract | The peroxisome proliferator-activated receptor γ (PPARγ) plays essential roles in adipogenesis and glucose homeostasis and is a molecular target of insulin-sensitizing drugs1–3. Although the ability of PPARγ agonists to antagonize inflammatory responses by transrepression of nuclear factor kappaB (NF-κB) target genes is linked to anti-diabetic4 and antiatherogenic actions5, the mechanisms remain poorly understood. Here we report the identification of a molecular pathway by which PPARγ represses transcriptional activation of inflammatory response genes in macrophages. The initial step of this pathway involves ligand-dependent sumoylation of the PPARγ ligand-binding domain, which targets PPARγ to nuclear receptor co-repressor (NCoR)/histone deacetylase-3 (HDAC3) complexes on inflammatory gene promoters. This in turn prevents recruitment of the ubiquitylation/19S proteosome machinery that normally mediates the signal-dependent removal of corepressor complexes required for gene activation. As a result, NCoR complexes are not cleared from the promoter and target genes are maintained in a repressed state. This mechanism provides an explanation for how an agonist-bound nuclear receptor can be converted from an activator of transcription to a promoter-specific repressor of NF-κB target genes that regulate immunity and homeostasis. |
| Related Links | http://dx.doi.org/10.1038/nature03988 |
| Ending Page | 763 |
| Page Count | 5 |
| Starting Page | 759 |
| File Format | |
| ISSN | 00280836 |
| e-ISSN | 14764687 |
| Journal | Nature |
| Issue Number | 7059 |
| Volume Number | 437 |
| Language | English |
| Publisher Date | 2005-09-29 |
| Access Restriction | Open |
| Subject Keyword | General Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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