Functional evidence for retinoid X receptor (RXR) as a nonsilent partner in the thyroid hormone receptor/RXR heterodimer.
Many members of the thyroid hormone/retinoid receptor subfamily (type II nuclear receptors) function as heterodimers with the retinoid X receptor (RXR). In heterodimers which are referred to as permissive, such as peroxisome proliferator activated receptor/RXR, both partners can bind cognate ligands and elicit ligand-dependent transactivation. In contrast, the thyroid hormone receptor (TR)/RXR heterodimer is believed to be nonpermissive, where RXR is thought to be incapable of ligand binding and is often referred to as a silent partner. In this report, we used a sensitive derepression assay system that we developed previously to reexamine the TR/RXR interrelationship. We provide functional evidence suggesting that in a TR/RXR heterodimer, the RXR component can bind its ligand in vivo. Ligand binding by RXR does not appear to directly activate the TR/RXR heterodimer; instead, it leads to a (at least transient or dynamic) dissociation of a cellular inhibitor(s)/corepressor(s) from its TR partner and thus may serve to modulate unliganded TR-mediated repression and/or liganded TR-mediated activation. Our results argue against the current silent-partner model for RXR in the TR/RXR heterodimer and reveal an unexpected aspect of cross regulation between TR and RXR.
Li
Dangsheng
D
Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.
Li
Tong
T
Wang
Fang
F
Tian
Heather
H
Samuels
Herbert H
HH
D000077556:Alitretinoin; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000077610:Bexarotene; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D017405:Herpes Simplex Virus Protein Vmw65 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism
D016588:Anticarcinogenic Agents; D004268:DNA-Binding Proteins; D017405:Herpes Simplex Virus Protein Vmw65; D008024:Ligands; D009687:Nuclear Proteins; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D013764:Tetrahydronaphthalenes; D014157:Transcription Factors; D014284:Triiodothyronine; D000077556:Alitretinoin; D014212:Tretinoin; D000077610:Bexarotene