title: Dimerization interfaces of v-erbA homodimers and heterodimers with retinoid X receptor alpha.
abstract: The oncoprotein v-ErbA, a member of the zinc finger transcription factor superfamily, is a mutated version of thyroid hormone receptor alpha1 that is virtually incapable of binding T3. v-ErbA and other members of this family can bind as homodimers and heterodimers with retinoid X receptors to specific DNA sequences arranged as direct, inverted, or everted repeats. At least two regions in the C-terminal domain, the I box (10 and 11 helices in v-ErbA and thyroid hormone receptors) and the 20-amino acid region are involved in dimerization. However, it has not been entirely understood how these receptors dimerize on differently oriented core motifs and whether the domain(s) responsible for homodimerization and heterodimerization are identical. Therefore, deletions of the entire 20-amino acid region, the 10 helix, the 11 helix, and point mutations within these regions of v-ErbA were made by site-directed mutagenesis. The mutant proteins were tested for their ability to form v-ErbA homodimers and heterodimers with retinoid X receptor alpha on differently oriented core motifs by electrophoretic mobility shift assay. Transient transfections were performed to determine the dominant negative activity of the v-ErbA mutants. The data indicate that different dimerization interfaces are used for v-ErbA homodimerization and heterodimerization with retinoid X receptor alpha, and different dimerization interfaces are used on differently oriented core motifs. The data are of general interest because the information improves our understanding of the role of these dimerization interfaces in the mechanism of action not only of v-ErbA but also of other members of the superfamily.
authors.affiliation: Division of Endocrinology and Metabolism, University of Mississippi Medical Center and G. V. Montgomery Veterans Administration Medical Center, Jackson, Mississippi 39216, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Shen
authors.forename: J S
authors.initials: JS
authors.lastname: Subauste
mesh_terms: D000595:Amino Acid Sequence; D004247:DNA / Q000378:metabolism; D019281:Dimerization; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D018774:Oncogene Proteins v-erbA / Q000737:chemistry* / Q000502:physiology; D017433:Protein Structure, Secondary; D018168:Receptors, Retinoic Acid / Q000737:chemistry*; D020218:Response Elements; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D018774:Oncogene Proteins v-erbA; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D014157:Transcription Factors; D004247:DNA