CELLULAR responsiveness to retinoic acid and its metabolites is conferred through two structurally and pharmacologically distinct1 families of receptors: the retinoic acid receptors (RAR)2,3 and the retinoid X receptors (RXR)1. Here we report that the transcriptional activity of RAR and RXR can be reciprocally modulated by direct interactions between the two proteins. RAR and RXR have a high degree of cooperativity in binding to target DNA, consistent with previous reports indicating that the binding of either RAR or RXR to their cognate response elements is enhanced by factors present in nuclear extracts4,5. RXR also interacts directly with and enhances the binding of nuclear receptors conferring responsiveness to vitamin D3 and thyroid hormone T3; the DNA-binding activities of these receptors are also stimulated by the presence of nuclear extracts6–9. Together these data indicate that RXR has a central role in multiple hormonal signalling pathways.
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Kliewer, S., Umesono, K., Mangelsdorf, D. et al. Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling. Nature 355, 446–449 (1992). https://doi.org/10.1038/355446a0
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