Thyroid Hormone Regulation of Apoptosis Induced by Retinoic Acid in Promyeloleukemic HL-60 Cells: Studies with Retinoic Acid Receptor-Specific and Retinoid × Receptor-Specific Ligands

Thyroid ◽  
2000 ◽  
Vol 10 (12) ◽  
pp. 1023-1034 ◽  
Author(s):  
Masahiro Hara ◽  
Satoru Suzuki ◽  
Jun-ichirou Mori ◽  
Koh Yamashita ◽  
Mieko Kumagai ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Retinoic Acid Receptor ◽  
Hormone Regulation ◽  
Retinoid Receptor ◽  
Acid Receptor

Dual regulatory role for thyroid-hormone receptors allows control of retinoic-acid receptor activity

Nature ◽  
1989 ◽  
Vol 340 (6235) ◽  
pp. 653-656 ◽  
Author(s):  
Gerhart Graupner ◽  
Ken N. Wills ◽  
Maty Tzukerman ◽  
Xiao-kun Zhang ◽  
Magnus Pfahl
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Hormone Receptors ◽  
Retinoic Acid Receptor ◽  
Receptor Activity ◽  
Regulatory Role ◽  
Thyroid Hormone Receptors ◽  
Acid Receptor

scholarly journals Effect of retinoid status on α, β and γ retinoic acid receptor mRNA levels in various rat tissues

1992 ◽  
Vol 286 (3) ◽  
pp. 755-760 ◽  
Author(s):  
S Kato ◽  
H Mano ◽  
T Kumazawa ◽  
Y Yoshizawa ◽  
R Kojima ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Vitamin A ◽  
Retinoic Acid Receptor ◽  
Rat Tissues ◽  
Mrna Levels ◽  
Acid Receptor ◽  
Beta Gene

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)alpha, RAR beta and RAR gamma mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RAR alpha and RAR gamma mRNAs, the level of RAR beta transcripts was greatly decreased in various tissues of vitamin A-deficient rats, but was restored rapidly to a normal level after administration of retinoic acid. Retinol also restored the RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RAR beta mRNA levels seemed to require a threshold serum retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RAR beta transcripts (2-15-fold) when compared with the control levels of RAR beta mRNA, although the levels of RAR alpha and RAR gamma mRNAs were not affected. Vitamin D and thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific ligand regulation of RAR beta gene expression in intact animals. The altered levels of RAR beta according to retinoid status may affect retinoid-inducible gene expression.

scholarly journals Activation of the phosphoenolpyruvate carboxykinase gene retinoic acid response element is dependent on a retinoic acid receptor/coregulator complex.

1992 ◽  
Vol 12 (12) ◽  
pp. 5527-5535 ◽  
Author(s):  
R K Hall ◽  
D K Scott ◽  
E L Noisin ◽  
P C Lucas ◽  
D K Granner
Keyword(s):  
Retinoic Acid ◽  
Transcriptional Control ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Mutational Analysis ◽  
Retinoic Acid Receptor ◽  
Retinoid Receptor ◽  
Response Element ◽  
Acid Receptor ◽  
Receptor Alpha ◽  
Retinoic Acid Response Element

The accessory factor 1 (AF1) element is an upstream transcriptional control region that plays a role in the response of the phosphoenolpyruvate carboxykinase (PEPCK) gene to both glucocorticoids and retinoic acid. We demonstrate here that retinoic acid receptor alpha (RAR alpha) binds to a sequence within the AF1 element, TGACCT (site B), that is a consensus retinoic acid response element (RARE) half-site. A similar DNA sequence, TGGCCG (site C), located 1 bp downstream of site B, is not involved in the binding of RAR alpha monomers or dimers but is required for the constitution of a functional RARE. Site C is also required for the formation of a complex involving RAR alpha and a liver nuclear factor designated CR, for coregulator. Mutational analysis of the AF1 element shows that the RAR alpha/CR complex is the trans-acting unit that mediates the retinoic acid response of the PEPCK gene. Another member of the retinoid receptor family, retinoid X receptor alpha (RXR alpha), can also form a complex with RAR alpha and the AF1 element. Several observations, including the observation that RXR alpha antibody interacts with CR, indicate that RXR alpha and CR are identical or closely related proteins. Through RXR alpha forms a complex with RAR alpha and the AF1 element, we demonstrate that the AF1 element is functionally distinguishable from a retinoid X response element. Taken together, our results show that the AF1 element contains an RARE that mediates a retinoic acid response by binding an RAR alpha/coregulator complex; this coregulator is presumably RXR alpha.

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.

scholarly journals Retinoic Acid Receptor and Retinoid × Receptor in Ductal Carcinomain situand Intraductal Proliferative Lesions of the Human Breast

2000 ◽  
Vol 91 (11) ◽  
pp. 1169-1176 ◽  
Author(s):  
Naohiro Ariga ◽  
Takuya Moriya ◽  
Takashi Suzuki ◽  
Michio Kimura ◽  
Noriaki Ohuchi ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Human Breast ◽  
Retinoid Receptor ◽  
Acid Receptor

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 Identification and characterization of a functional retinoic acid/thyroid hormone-response element upstream of the human insulin gene enhancer

1995 ◽  
Vol 309 (3) ◽  
pp. 863-870 ◽  
Author(s):  
A R Clark ◽  
M E Wilson ◽  
N J M London ◽  
R F L James ◽  
K Docherty
Keyword(s):  
Retinoic Acid ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Retinoic Acid Receptor ◽  
Nuclear Hormone Receptor ◽  
Insulin Gene ◽  
Acid Receptor ◽  
Trans Retinoic Acid ◽  
Human Insulin Gene ◽  
All Trans Retinoic Acid

A deletion analysis of the human insulin gene extending to 2 kb upstream of the transcription start site provided evidence of regulatory sequences located upstream of the insulin-linked polymorphic region (ILPR). Within this ILPR-distal region is a sequence (Ink, for insulin kilobase upstream) which contains three potential nuclear hormone-receptor half-sites, closely matching the consensus sequence AGGTCA. These sequences are arranged as a palindromic element with zero spacing over-lapping a direct repeat with 2 bp spacing. The Ink sequence was used in electrophoretic mobility-shift assays within nuclear extracts from COS-7 cells overexpressing the vitamin D, thyroid hormone or retinoic acid receptors, or from an insulin-expressing hamster cell line, HIT-T15. These studies suggest that the insulin-expressing cell line contains thyroid hormone and retinoic acid receptors at least, and that these receptors are able to recognize the Ink sequence. Three copies of the Ink sequence were placed upstream of the thymidine kinase promoter and firefly luciferase reporter gene. In COS-7 cells expressing the appropriate nuclear hormone receptor, this construct was responsive to both thyroid hormone (18-fold) and all-trans-retinoic acid (31-fold). In HIT-T15 cells the same construct responded to all-trans-retinoic acid, but not to thyroid hormone. Within the context of a 2 kb insulin gene fragment, the Ink sequence was shown to be activated by retinoic acid and by the retinoic acid receptor, but acted as a negative element in the presence of both retinoic acid and the retinoic acid receptor. Mutagenesis studies demonstrated that the palindromic sequence was important for the retinoic acid response, and for binding of complexes containing retinoic acid receptor. In human islets of Langerhans, retinoic acid was shown to stimulate insulin mRNA levels. These results demonstrate that a functional nuclear hormone-receptor-response element is located upstream of the human ILPR. As retinoic acid and thyroid hormone are frequently involved in developmental regulatory processes, it is possible that this element may be important in the process of islet cell differentiation.

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