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Molecular and Cellular Biology, August 2002, p. 5782-5792, Vol. 22, No. 16
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.16.5782-5792.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Functional Evidence for Retinoid X Receptor (RXR) as a Nonsilent Partner in the Thyroid Hormone Receptor/RXR Heterodimer

Dangsheng Li, Tong Li, Fang Wang, Heather Tian, and Herbert H. Samuels*

Departments of Pharmacology and Medicine, New York University School of Medicine, New York, New York 10016

Received 20 December 2001/ Returned for modification 31 January 2002/ Accepted 15 May 2002

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.

* Corresponding author. Mailing address: Departments of Pharmacology and Medicine, New York University School of Medicine, 550 First Ave., New York, NY 10016. Phone: (212) 263-6279. Fax: (212) 263-7701. E-mail: herbert.samuels{at}med.nyu.edu.

Molecular and Cellular Biology, August 2002, p. 5782-5792, Vol. 22, No. 16
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.16.5782-5792.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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