Abstract
RETINOID X receptor (RXR) plays a central role in the regulation of many intracellular receptor signalling pathways1 and can mediate ligand-dependent transcription, acting as a homodimer or as a heterodimer1–6. 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 peroxi-some 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 SMRT7, 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.
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Lala, D., Mukherjee, R., Schulman, I. et al. Activation of specific RXR heterodimers by an antagonist of RXR homodimers. Nature 383, 450–453 (1996). https://doi.org/10.1038/383450a0
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DOI: https://doi.org/10.1038/383450a0
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