Ligand-triggered stabilization of vitamin D Receptor/Retinoid X receptor heterodimer conformations on DR4-type response elements
Identifieur interne : 000A93 ( Main/Exploration ); précédent : 000A92; suivant : 000A94Ligand-triggered stabilization of vitamin D Receptor/Retinoid X receptor heterodimer conformations on DR4-type response elements
Auteurs : Marcus Quack [Allemagne] ; Carsten Carlberg [Allemagne]Source :
- Journal of Molecular Biology [ 0022-2836 ] ; 2000.
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Abstract
Nuclear receptors integrate an incoming signal in the form of a nuclear hormone by undergoing a conformational change that results via co-activator proteins in an activation of the basal transcriptional machinery. The vitamin D3 receptor is the nuclear receptor for 1α,25-dihydroxy vitamin D3 (1α,25(OH)2D3) and is known to function as a heterodimer with the retinoid X receptor on DR3-type 1α,25(OH)2D3 response elements. Here, it could be demonstrated that DR4-type response elements are at least as effective as DR3-type 1α,25(OH)2D3 response elements. Gel shift clipping analysis showed that vitamin D3 receptor-retinoid X receptor heterodimers form in response to 1α,25(OH)2D3 and retinoid X receptor ligands, the pan-agonist 9-cis retinoic acid (9cRA) and the retinoid X receptor-selective retinoid CD2425, different conformations on the DR4-type element of the rat Pit-1 gene. Interestingly, on this response element the heterodimeric complexes of retinoid X receptor with the thyroid hormone receptor, the retinoic acid receptor and the benzoate ester receptor also displayed characteristic individual ligand-dependent complex formation. On the level of complex formation, utilizing DNA affinity and functional assays, only vitamin D3 receptor-retinoid X receptor heterodimers showed a synergistic interaction of both ligands. However, the sensitivity of vitamin D3 receptor-retinoid X receptor heterodimers to 1α,25(OH)2D3 was found to be much higher than to retinoid X receptor ligands. Taken together, this study demonstrates a unique interaction potential of vitamin D3 receptor and retinoid X receptor but also establishes DR4-type response elements as multi-functional DNA binding sites with a potential to integrate various hormone signalling pathways.
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DOI: 10.1006/jmbi.2000.3499
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The vitamin D3 receptor is the nuclear receptor for 1α,25-dihydroxy vitamin D3 (1α,25(OH)2D3) and is known to function as a heterodimer with the retinoid X receptor on DR3-type 1α,25(OH)2D3 response elements. Here, it could be demonstrated that DR4-type response elements are at least as effective as DR3-type 1α,25(OH)2D3 response elements. Gel shift clipping analysis showed that vitamin D3 receptor-retinoid X receptor heterodimers form in response to 1α,25(OH)2D3 and retinoid X receptor ligands, the pan-agonist 9-cis retinoic acid (9cRA) and the retinoid X receptor-selective retinoid CD2425, different conformations on the DR4-type element of the rat Pit-1 gene. Interestingly, on this response element the heterodimeric complexes of retinoid X receptor with the thyroid hormone receptor, the retinoic acid receptor and the benzoate ester receptor also displayed characteristic individual ligand-dependent complex formation. On the level of complex formation, utilizing DNA affinity and functional assays, only vitamin D3 receptor-retinoid X receptor heterodimers showed a synergistic interaction of both ligands. However, the sensitivity of vitamin D3 receptor-retinoid X receptor heterodimers to 1α,25(OH)2D3 was found to be much higher than to retinoid X receptor ligands. Taken together, this study demonstrates a unique interaction potential of vitamin D3 receptor and retinoid X receptor but also establishes DR4-type response elements as multi-functional DNA binding sites with a potential to integrate various hormone signalling pathways.</div></front></TEI><affiliations><list><country><li>Allemagne</li></country><region><li>District de Düsseldorf</li><li>Rhénanie-du-Nord-Westphalie</li></region><settlement><li>Düsseldorf</li></settlement></list><tree><country name="Allemagne"><region name="Rhénanie-du-Nord-Westphalie"><name sortKey="Quack, Marcus" sort="Quack, Marcus" uniqKey="Quack M" first="Marcus" last="Quack">Marcus Quack</name></region><name sortKey="Carlberg, Carsten" sort="Carlberg, Carsten" uniqKey="Carlberg C" first="Carsten" last="Carlberg">Carsten Carlberg</name><name sortKey="Carlberg, Carsten" sort="Carlberg, Carsten" uniqKey="Carlberg C" first="Carsten" last="Carlberg">Carsten Carlberg</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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