Activation of specific RXR heterodimers by an antagonist of RXR homodimers.

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

Nature

journal_title

Nature

authors

Lala DS,Mukherjee R,Schulman IG,Koch SS,Dardashti LJ,Nadzan AM,Croston GE,Evans RM,Heyman RA

doi

10.1038/383450a0

subject

Has Abstract

pub_date

1996-10-03 00:00:00

pages

450-3

issue

6599

eissn

0028-0836

issn

1476-4687

journal_volume

383

pub_type

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