Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling

• Published in: Nature (London) Vol. 355; no. 6359; pp. 446 - 449
• Main Authors: KLIEWER, S. A, UMESONO, K, MANGELSDORF, D. J, EVANS, R. M
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 30-01-1992
• Subjects: Animals; Biological and medical sciences; Carrier Proteins - genetics; Carrier Proteins - physiology; Cell Line; Cell receptors; Cell structures and functions; Chloramphenicol O-Acetyltransferase - genetics; Chloramphenicol O-Acetyltransferase - metabolism; Cholecalciferol - pharmacology; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Kinetics; Luciferases - genetics; Luciferases - metabolism; Molecular and cellular biology; Nuclear Proteins - metabolism; Receptors, Calcitriol; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Receptors, Retinoic Acid; Receptors, Steroid - physiology; Receptors, Thyroid Hormone - physiology; Recombinant Fusion Proteins - metabolism; Restriction Mapping; Retinoid X Receptors; Signal Transduction; Transcription Factors; Transcription, Genetic - drug effects; Transfection; Tretinoin - metabolism; Tretinoin - pharmacology; Triiodothyronine - pharmacology; Signal transduction; Transcription; Cell nucleus; Thyroid hormone; Gene expression; Colecalciferol; Hormonal receptor
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/355446a0

Cellular responsiveness to retinoic acid and its metabolites is conferred through two structurally and pharmacologically distinct families of receptors: the retinoic acid receptors (RAR) and the retinoid X receptors (RXR). Here we report that the transcriptional activity of RAR and RXR can be reciprocally modulated by direct interactions between the two proteins. RAR and RXR have a high degree of cooperativity in binding to target DNA, consistent with previous reports indicating that the binding of either RAR or RXR to their cognate response elements is enhanced by factors present in nuclear extracts. RXR also interacts directly with and enhances the binding of nuclear receptors conferring responsiveness to vitamin D3 and thyroid hormone T3; the DNA-binding activities of these receptors are also stimulated by the presence of nuclear extracts. Together these data indicate that RXR has a central role in multiple hormonal signalling pathways.