Retinoic Acid Receptor–Related Orphan Receptor Alpha–Enhanced Thyroid Hormone Receptor–Mediated Transcription Requires Its Ligand Binding Domain Which Is Not, by Itself, Sufficient: Possible Direct Interaction of Two Receptors

Thyroid ◽  
2009 ◽  
Vol 19 (8) ◽  
pp. 893-898 ◽  
Author(s):  
Chun-Hong Qiu ◽  
Wataru Miyazaki ◽  
Toshiharu Iwasaki ◽  
Marina Londoño ◽  
Kingsley Ibhazehiebo ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Ligand Binding ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Direct Interaction ◽  
Orphan Receptor ◽  
Acid Receptor ◽  
Receptor Alpha

scholarly journals Alteration of Cerebellar Neurotropin Messenger Ribonucleic Acids and the Lack of Thyroid Hormone Receptor Augmentation by staggerer-Type Retinoic Acid Receptor-Related Orphan Receptor-α Mutation

Endocrinology ◽  
2007 ◽  
Vol 148 (4) ◽  
pp. 1745-1753 ◽  
Author(s):  
Chun-Hong Qiu ◽  
Noriaki Shimokawa ◽  
Toshiharu Iwasaki ◽  
Ishwar S. Parhar ◽  
Noriyuki Koibuchi
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Thyroid Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Orphan Receptor ◽  
Granule Cell Layer ◽  
Mrna Levels ◽  
Response Element ◽  
Altered Expression ◽  
Acid Receptor

The mutant mouse staggerer (sg) harbors a deletion within the gene encoding the retinoic acid receptor-related orphan receptor-α (RORα). Homozygotes show aberrant cerebellar development. However, the mechanisms responsible for the cerebellar defect are still poorly understood. In the present study, the involvement of neurotropins (NTs), including nerve growth factor, brain-derived neurotropic factor, NT-3 and NT-4/5, and their receptors, which play a crucial role in brain development, on the cerebellar defects of sg mice was studied by semiquantitative RT-PCR and in situ hybridization histochemistry. An evident alteration of these mRNA levels was observed in both heterozygotes and homozygotes. Such difference was most evident in the internal granule cell layer. Because the changes in NT expression as well as morphological alterations in sg cerebellum are similar to those in hypothyroid animals, the effect of mutant RORα (RORsg) on transcriptional regulation through the thyroid hormone (TH) response element or the ROR response element (RORE) was then studied. RORsg neither activated the transcription through RORE nor suppressed RORα-induced transcription, indicating that it does not function as a dominant negative inhibitor. On the other hand, although wild-type RORα augmented TH receptor (TR)α1/β1-mediated transcription through various TH response elements, RORsg was not effective in augmenting TR action. These results suggest that the cerebellar defect of the sg mouse is partly caused by the altered expression of NTs and the lack of augmentation of TR-mediated transcription by RORα as well as the absence of RORα action through RORE.

scholarly journals Myb-Ets fusion oncoprotein inhibits thyroid hormone receptor/c-ErbA and retinoic acid receptor functions: a novel mechanism of action for leukemogenic transformation by E26 avian retrovirus.

1996 ◽  
Vol 16 (11) ◽  
pp. 6338-6351 ◽  
Author(s):  
A Rascle ◽  
N Ferrand ◽  
O Gandrillon ◽  
J Samarut
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Biological Response ◽  
Erythroid Differentiation ◽  
Acid Receptor ◽  
Hormone Response Elements ◽  
Differentiation Stage

The E26 and avian erythroblastosis virus (AEV) avian retroviruses induce acute leukemia in chickens. E26 can block both erythroid and myeloid differentiation at an early multipotent stage. Moreover, E26 can block erythroid differentiation at the erythroid burst-forming unit/erythroid CFU (BFU-E/CFU-E) stage, which also corresponds to the differentiation stage blocked by AEV. AEV carries two oncogenes, v-erbA and v-erbB, whereas E26 encodes a single 135-kDa Gag-Myb-Ets fusion oncoprotein. v-ErbA is responsible for the erythroid differentiation arrest through negative interferences with both the retinoic acid receptor (RAR) and the thyroid hormone receptor (T3R/c-ErbA). We investigated whether Myb-Ets could block erythroid differentiation in a manner similar to v-ErbA. We show here that Myb-Ets inhibits both RAR and c-ErbA activities on specific hormone response elements in transient-expression assays. Moreover, Myb-Ets abrogates the inactivation of transcription factor AP-1 by RAR and T3R, another feature shared with v-ErbA. Myb-Ets also antagonizes the biological response of erythrocytic progenitor cells to retinoic acid and T3. Analysis of a series of mutants of Myb-Ets reveals that the domains of the oncoprotein involved in these inhibitory activities are the same as those involved in oncogenic transformation of hematopoietic cells. These data demonstrate that the Myb-Ets oncoprotein shares properties with the v-ErbA oncoprotein and that inhibition of ligand-dependent RAR and c-ErbA functions by Myb-Ets is responsible for blocking the differentiation of hematopoietic progenitors.

scholarly journals tau4/tau c/AF-2 of the thyroid hormone receptor relieves silencing of the retinoic acid receptor silencer core independent of both tau4 activation function and full dissociation of corepressors.

1997 ◽  
Vol 17 (8) ◽  
pp. 4259-4271 ◽  
Author(s):  
A Baniahmad ◽  
D Thormeyer ◽  
R Renkawitz
Keyword(s):  
Amino Acids ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Thyroid Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Activation Function ◽  
Acid Receptor ◽  
C Terminus

Members of the thyroid hormone (TR)-retinoic acid receptor (RAR) subfamily of nuclear hormone receptors silence gene expression in the absence of hormone. Addition of cognate ligands leads to dissociation of corepressors, association of coactivators, and transcriptional activation. Here, we used the hRAR alpha silencer core, which encompasses the ligand binding domain, including receptor regions D and E of RAR alpha without the activation function called tau4/tau c/AF-2 and without the F region, to analyze the mechanisms by which transcriptional silencing is relieved. Although the RAR silencer core is able to bind ligand, it acts as a constitutive transcriptional silencer. We have fused various small activation domains to the C terminus of the silencer core and analyzed hormone-dependent changes in receptor function. We show that nine amino acids derived from the hTRbeta are sufficient to transform the RAR silencer core into a hormone-dependent activator. Lengthening the linker between the silencer core and these nine amino acids is not critical for mediating ligand-induced relief of silencing and activation. In addition, we show that a transactivation function at the C terminus is not required for relief of silencing by the hormone, but it is required for transcriptional activation. Furthermore, we created functional silencer fusions which lose their repressive function upon addition of hormone, although the corepressors SMRT and N-CoR remain attached to the receptor.

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