Journal article
Interdomain communication regulating ligand binding by PPAR-γ
Nature (London), v 396(6709), pp 377-380
26 Nov 1998
PMID: 9845075
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Binding to receptors in the cell nucleus is crucial for the action of lipophilic hormones and ligands. PPAR-γ (for peroxisome proliferator-activated receptor) is a nuclear hormone receptor that mediates adipocyte differentiation, and modulates insulin sensitivity, cell proliferation and inflammatory processes,. PPAR-γ ligands have been implicated in the development of atherogenic foam cells and as potential cancer treatments. Transcriptional activity of PPAR-γ is induced by binding diverse ligands, including natural fatty acid derivatives, antidiabetic thiazolidinediones, and non-steroidal anti-inflammatory drugs. Ligand binding by PPAR-γ, as well as by the entire nuclear-receptor superfamily, is an independent property of the carboxy-terminal ligand-binding domain (LBD) of the receptor,. Here we show that ligand binding by PPAR-γ is regulated by intramolecular communication between its amino-terminal A/B domain and its carboxy-terminal LBD. Modification of the A/B domain, for example by physiological phosphorylation by MAP kinase, reduces ligand-binding affinity, thus negatively regulating the transcriptional and biological functions of PPAR-γ. The ability of the A/B domain to regulate ligand binding has important implications for the evaluation and mechanism of action of potentially therapeutic ligands that bind PPAR-γ and that are likely to extend to other members of the nuclear-receptor superfamily.
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Details
- Title
- Interdomain communication regulating ligand binding by PPAR-γ
- Creators
- Mitchell A Lazar - University of PennsylvaniaDalei Shao - University of PennsylvaniaShamina M Rangwala - Faculty (United Kingdom)Shannon T Bailey - Division of Endocrinology, Diabetes, and Metabolism, Department of MedicineSamuel L Krakow - Faculty (United Kingdom)Mauricio J Reginato - Philadelphia University
- Publication Details
- Nature (London), v 396(6709), pp 377-380
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000077204000052
- Scopus ID
- 2-s2.0-0032569902
- Other Identifier
- 991020099411304721
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- Web of Science research areas
- Biochemistry & Molecular Biology