Activation of specific RXR heterodimers by an antagonist of RXR homodimers
| Autor: | Ira G. Schulman, Ronald M. Evans, Glenn E. Croston, Stacie S. Canan Koch, Dardashti Laura J, Deepak S. Lala, Richard A. Heyman, Ranjan Mukherjee, A. M. Nadzan |
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| Rok vydání: | 1996 |
| Předmět: |
Agonist
Tetrahydronaphthalenes Transcription Genetic Receptors Retinoic Acid medicine.drug_class Receptors Cytoplasmic and Nuclear Retinoid X receptor Biology Ligands Transfection environment and public health Retinoids Transcription (biology) Tumor Cells Cultured medicine Enzyme-linked receptor Drosophila Proteins Nuclear Receptor Co-Repressor 2 Nuclear receptor co-repressor 2 TATA-Binding Protein Associated Factors Multidisciplinary Retinoid X receptor alpha TATA-Box Binding Protein Nicotinic Acids DNA-Binding Proteins Repressor Proteins Retinoic acid receptor Retinoid X Receptors Gene Expression Regulation Biochemistry Trans-Activators Transcription Factor TFIID Dimerization Transcription Factors |
| Zdroj: | Nature. 383:450-453 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/383450a0 |
| Popis: | Retinoid X receptor (RXR) plays a central role in the regulation of many intracellular receptor signalling pathways and can mediate ligand-dependent transcription, acting as a homodimer or as a heterodimer. Here we identify an antagonist towards RXR homodimers which also functions as an agonist when RXR is paired as a heterodimer to specific partners, including peroxisome proliferator-activated receptor and retinoic acid receptor. This dimer-selective ligand confers differential interactions on the transcription machinery: the antagonist promotes association with TAF110 (TATA-binding protein (TBP)-associated factor 110) and the co-repressor SMRT, but not with TBP, and these properties are distinct from pure RXR agonists. This unique class of RXR ligands will provide a means to control distinct target genes at the level of transcription and allow the development of retinoids with a new pharmacological action. |
| Databáze: | OpenAIRE |
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