Abstract:
: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.
journal_name
Naturejournal_title
Natureauthors
Lala DS,Mukherjee R,Schulman IG,Koch SS,Dardashti LJ,Nadzan AM,Croston GE,Evans RM,Heyman RAdoi
10.1038/383450a0subject
Has Abstractpub_date
1996-10-03 00:00:00pages
450-3issue
6599eissn
0028-0836issn
1476-4687journal_volume
383pub_type
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