title: Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.
abstract: Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.
authors.affiliation: Cancer Center, La Jolla Cancer Research Foundation, California 92037.
authors.forename: J M
authors.initials: JM
authors.lastname: Lehmann
authors.forename: X K
authors.initials: XK
authors.lastname: Zhang
authors.forename: G
authors.initials: G
authors.lastname: Graupner
authors.forename: M O
authors.initials: MO
authors.lastname: Lee
authors.forename: T
authors.initials: T
authors.lastname: Hermann
authors.forename: B
authors.initials: B
authors.lastname: Hoffmann
authors.forename: M
authors.initials: M
authors.lastname: Pfahl
mesh_terms: D000818:Animals; D001483:Base Sequence; D001667:Binding, Competitive; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000187:drug effects* / Q000235:genetics; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin / Q000494:pharmacology; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D018076:DNA, Complementary; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D014212:Tretinoin