Dimerization interfaces of thyroid hormone, retinoic acid, vitamin D, and retinoid X receptors.
A subclass of erbA-related nuclear receptors has been shown to require interaction with an auxiliary protein(s) from nuclear extract in order to achieve high affinity DNA binding in vitro. The retinoid X receptor recently has been demonstrated to be such an auxiliary protein as it enhances specific DNA binding by thyroid hormone receptors, retinoic acid receptors, and the vitamin D receptor. Mutation of a highly conserved 20-amino acid region within the ligand-binding domain of thyroid hormone receptor beta disrupts its physical association with auxiliary protein from JEG-3 cells as well as with recombinant retinoid X receptor beta. The homologous 20-amino acid regions from retinoic acid receptor alpha and the vitamin D receptor also are critical determinants of the heterodimeric interaction between these receptors and JEG-3 cell auxiliary protein as well as retinoid X receptor beta. However, the same region of retinoid X receptor beta appears to play a minor, if any, role in heterodimerization. In addition, transfection studies indicate that disruption of heterodimerization impairs the ability of these receptors to function as ligand-dependent transcriptional activators.
Rosen
E D
ED
Endocrinology Division, University of Michigan Medical Center, Ann Arbor 48109-0678.
Beninghof
E G
EG
Koenig
R J
RJ
D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D005810:Multigene Family; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors; D014162:Transfection; D014212:Tretinoin / Q000378:metabolism
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors; D014212:Tretinoin