Thyroid hormone receptors (TRs) and the oncoprotein v-erbA can heterodimerize with retinoid X receptor (RXR) on core motifs arranged as inverted repeats (IR0) which contain the consensus sequence AGGTCA. On this core motif, v-erbA can also form homodimers whereas TRs homodimerize very poorly. Therefore to obtain a better understanding of distinct homodimerization properties of TR alpha 1 as compared to those of v-erbA, we created chimeras between these two receptors and tested their abilities to homodimerize on IR0. We found that the enhanced homodimerization properties of v-erbA compared to those of TR alpha 1 on IR0 map to amino acids 107-156 in v-erbA/121-170 in TR alpha 1 (VT-2 chimera). Furthermore, functional studies on transient transfections showed that v-erbA-RXR heterodimers do not mediate the dominant negative activity of v-erbA on an inverted repeat response element. These data, in conjunction with our previous studies, indicate that v-erbA homodimers mediate the repressor activity of v-erbA on IR0.
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V-erba homodimers mediate the potent dominant negative activity of v-erba on everted repeats.
Mol Biol Rep
June 2004
G. V Montgomery Veterans Administration Medical Center and Division of Endocrinology and Metabolism, University of Mississippi, Jackson, MS 39216, USA.
The oncoprotein v-erbA is a mutated form of TRalpha1 that is unable to bind thyroid hormone (T3). V-erbA homodimerizes or heterodimerizes with retinoid X receptor (RXR) on core motifs arranged as direct, everted, or inverted repeats (DRs, ERs, or IRs). We created a series of v-erbA mutants in order to obtain a better understanding of the role of v-erbA homodimers versus v-erbA-RXR heterodimers in the dominant negative activity of v-erbA on ERs (the most potent v-erbA response elements).
View Article and Find Full Text PDFDimerization of v-erbA on inverted repeats.
Biochem Biophys Res Commun
May 2002
Division of Endocrinology and Metabolism, Department of Medicine, G.V. Montgomery Veterans Administration Medical Center, University of Mississippi, Jackson, MS 39216, USA.
Thyroid hormone receptors (TRs) and the oncoprotein v-erbA can heterodimerize with retinoid X receptor (RXR) on core motifs arranged as inverted repeats (IR0) which contain the consensus sequence AGGTCA. On this core motif, v-erbA can also form homodimers whereas TRs homodimerize very poorly. Therefore to obtain a better understanding of distinct homodimerization properties of TR alpha 1 as compared to those of v-erbA, we created chimeras between these two receptors and tested their abilities to homodimerize on IR0.
View Article and Find Full Text PDFDimerization interfaces of v-erbA homodimers and heterodimers with retinoid X receptor alpha.
J Biol Chem
December 2000
Division of Endocrinology and Metabolism, University of Mississippi Medical Center and G. V. Montgomery Veterans Administration Medical Center, Jackson, Mississippi 39216, USA.
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.
View Article and Find Full Text PDFCharacterization of the DNA-binding and dominant negative activity of v-erbA homodimers.
Mol Endocrinol
September 1998
Division of Endocrinology and Metabolism, University of Mississippi Medical Center, Jackson 39216, USA.
The oncoprotein v-erbA is a mutated form of thyroid hormone receptor alpha1 that is virtually incapable of binding T3. V-erbA is a dominant repressor of transcription induced by thyroid hormone receptors and retinoic acid receptors; however, the genetic targets of v-erbA that lead to oncogenesis are not known. Although v-erbA can bind as monomers and dimers to DNA containing the consensus sequence AGGTCA arranged as direct, inverted, or everted repeats, it is not known which sequence represents the optimal v-erbA-binding site.
View Article and Find Full Text PDFThe oncoprotein P75gag-v-erbA represses thyroid hormone induced transcription only via response elements containing palindromic half-sites.
Oncogene
August 1996
Department of Cellular and Molecular Biology, Karolinska Institute, Stockholm, Sweden.
The v-erbA oncoprotein P75gag-v-erbA, derived from the thyroid hormone receptor alpha (TR alpha), functions as a transdominant transcriptional repressor. The mechanism by which P75gag-v-erbA acts is however poorly characterized. Here, we show that repression of TR alpha mediated transcription by P75gag-v-erbA in transformed erythroblasts is dependent on the structure of the thyroid hormone response element to which it binds.
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