Heterodimerization among thyroid hormone receptor, retinoic acid receptor, retinoid X receptor, chicken ovalbumin upstream promoter transcription factor, and an endogenous liver protein.

Abstract

Thyroid hormone receptor (TR) binds to DNA as a monomer, homodimer, and heterodimer with nuclear proteins. We have confirmed that the TR can heterodimerize with retinoid X receptors (RXRs)-alpha and -beta, and have found that another member of the nuclear receptor superfamily, chicken ovalbumin upstream promoter transcription factor (COUP-TF), also formed heterodimers with the TR in the context of binding to a palindromic thyroid hormone-responsive element (TREp). The interaction between COUP-TF and the TR was confirmed using specific antibodies which supershifted the COUP-TF/TR DNA complexes. The complex between the TR and the major TR heterodimerization partner in liver was unaffected by antibodies to COUP-TF and RXR beta, but was supershifted by an anti-RXR alpha antibody, indicating that the liver protein is highly related to RXR alpha. Indeed, the TR/RXR and TR/liver protein heterodimers contact the same guanidine residues in TREp. The retinoic acid receptor (RAR) also heterodimerized with COUP-TF as well as with RXR alpha, RXR beta, and the TR heterodimerization partner in liver. In contrast to its ability to heterodimerize with the TR and RAR, we did not detect heterodimers between COUP-TF and either RXR alpha, RXR beta, or the liver nuclear protein in the context of binding to the TREp. These results show that the major TR heterodimerization partner in liver is highly related to RXR alpha, but that other nuclear receptors such as COUP-TF can heterodimerize with the TR and RAR, suggesting that selective protein-protein interactions may be involved in the tissue and target gene specificities of hormone action.

A Thyroid Hormone Receptor α Gene Mutation (P398H) Is Associated with Visceral Adiposity and Impaired Catecholamine-stimulated Lipolysis in Mice

“…Both PPAR and LXR heterodimerize with RXR as does TR. LXR has been reported to bind to a direct repeat with a 4-base gap (DR4) element, which may compete with TR binding (52,53). The P398H TR␣ mutant may differentially influence PPAR and LXR action by competing with RXR for heterodimerization, or by directly competing for DNA binding sites.…”

Thyroid hormone and retinoic acid induce the synthesis of insulin-like growth factor-binding protein-4 in prepubertal pig sertoli cells

“…Actually, the thyroid hormone receptor and RA receptor are structurally similar and can bind as homodimers or heterodimers to a single synthetic DNA response element, acting as ligand-dependent transcription factors (50,51). Both receptors belong to the steroid/thyroid hormone receptor superfamily, and interestingly one progesterone receptor-binding site has been localised in the rat IGFBP-4 gene 5 0 -flanking region (52).…”

Endogenous retinoid X receptors can function as hormone receptors in pituitary cells.

“…While retinoid-dependent transactivation by RXR is mediated in part by RXR homodimers (66), RXR is also able to form heterodimers with TR and VDR (7,18,36,37,46,48,64,65). In each case, target gene binding by the nuclear hormone receptor is greatly enhanced by its partnership with RXR.…”