Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors.
Thyroid hormones and retinoic acid function through nuclear receptors that belong to the steroid/thyroid-hormone receptor superfamily. Thyroid hormone receptors (TRs) and retinoic acid receptors (RARs) require auxiliary nuclear proteins for efficient DNA binding. Here we report that retinoid X receptors RXR alpha is one of these nuclear proteins. RXR alpha interacts both with TRs and with RARs, forming heterodimers in solution that strongly interact with a variety of T3/retinoic acid response elements. Transfection experiments show that RXR alpha can greatly enhance the transcriptional activity of TR and RAR at low retinoic acid concentrations that do not significantly activate RXR alpha itself. Thus, RXR alpha enhances the transcriptional activity of other receptors and its own ligand sensitivity by heterodimer formation. Our studies reveal a new subclass of receptors and a regulatory pathway controlling nuclear receptor activities by heterodimer formation.
Zhang
X K
XK
Cancer Center, La Jolla Cancer Research Foundation, California 92037.
Hoffmann
B
B
Tran
P B
PB
Graupner
G
G
Pfahl
M
M
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015723:Gene Library; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides; D010920:Placenta / Q000502:physiology; D016133:Polymerase Chain Reaction / Q000379:methods; D011247:Pregnancy; D014176:Protein Biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D015183:Restriction Mapping; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014284:Triiodothyronine; D014212:Tretinoin