Activation and repression by nuclear hormone receptors: hormone modulates an equilibrium between active and repressive states.
Transactivation-defective retinoid X and thyroid hormone receptors have been used to examine mechanisms of hormonal activation. Activation and repression of transcription by retinoid X and thyroid hormone receptors are shown to be mediated by physically distinct and functionally independent regions of the hormone binding domain. Nevertheless, the ability of receptors to respond to hormone requires communication between both functional domains. Deletion of the hormone-dependent transactivation function of the retinoid X receptor, the common subunit of heterodimeric nuclear receptors, significantly impairs hormone-dependent transcription by retinoic acid, thyroid hormone, and vitamin D receptors. The results indicate that receptors do not exist in static off and on conformations but that hormone alters an equilibrium between inactive and active states.
Schulman
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Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Juguilon
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H
Evans
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RM
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002762:Cholecalciferol / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008961:Models, Structural; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection; D014284:Triiodothyronine / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000096:biosynthesis
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D002762:Cholecalciferol; D001616:beta-Galactosidase