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Abstract
Cellular responsiveness to retinoic acid and its metabolites is conferred through
two structurally and pharmacologically distinct families of receptors: the retinoic
acid receptors (RAR) and the retinoid X receptors (RXR). 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 extracts.
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 extracts. Together
these data indicate that RXR has a central role in multiple hormonal signalling pathways.