title: Heterodimerization preferences of thyroid hormone receptor alpha isoforms.
abstract: Thyroid hormone receptors (TRs) are members of the steroid hormone receptor superfamily and are encoded by two different genes, alpha and beta. Three isoforms (alpha 1, alpha 2, and alpha 3) are created by alternative splicing of the TR alpha gene. In TR alpha 2 and alpha 3, the distal half of the putative dimerization domain is disrupted and the carboxy terminus of the protein is substituted with different amino acids. To evaluate the properties of these alterations in the dimerization region, DNA binding and dimerization of TR alpha isoforms were studied by electrophoretic mobility shift assays. TR alpha 1 formed a monomer or a homodimer on certain thyroid hormone responsive elements (TREs), whereas TR alpha 2 and alpha 3 did not bind effectively to any of the TREs studied. TR alpha 1 formed a heterodimer with 9-cis retinoic acid receptor alpha (RXR alpha) on all TREs studied. Although TR alpha 2 did not bind as a homodimer, it did bind as a heterodimer with RXR alpha to DR4 and MHC-TRE. TR alpha 3 bound as a heterodimer to a broader repertoire of TREs, including DR4, MHC, ME, and F2-TRE. These results indicate that the alterations in the dimerization region in TR alpha 2 and alpha 3 abrogated homodimer binding, but differentially affected heterodimerization with RXR alpha on various TREs.
authors.affiliation: Department of Endocrinology and Metabolism, Nagoya University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nagaya
authors.forename: Y
authors.initials: Y
authors.lastname: Nomura
authors.forename: M
authors.initials: M
authors.lastname: Fujieda
authors.forename: H
authors.initials: H
authors.lastname: Seo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001704:Biopolymers; D018076:DNA, Complementary; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011485:Protein Binding; D011988:Receptors, Thyroid Hormone / Q000235:genetics*
chemical_list: D001704:Biopolymers; D018076:DNA, Complementary; D011988:Receptors, Thyroid Hormone