Hormone-Dependent Transcriptional Activation by Thyroid Hormone Receptors: Functional Homology with Steroid Hormone Receptors

1989 ◽  
pp. 35-43
Author(s):  
S. M. Hollenberg ◽  
C. C. Thompson ◽  
R. M. Evans
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Functional Homology

scholarly journals Isoform-Specific Transcriptional Regulation by Thyroid Hormone Receptors: Hormone-Independent Activation Operates through a Steroid Receptor Mode of Coactivator Interaction

2001 ◽  
Vol 15 (7) ◽  
pp. 1170-1185 ◽  
Author(s):  
Zhihong Yang ◽  
Martin L. Privalsky
Keyword(s):  
Thyroid Hormone ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Steroid Hormone ◽  
Expression Patterns ◽  
Steroid Receptor ◽  
Steroid Hormone Receptors ◽  
Thyroid Hormone Receptors ◽  
Interaction Domain ◽  
Specific Expression

Abstract Thyroid hormone receptors (T3Rs) are hormone-regulated transcription factors that play important roles in vertebrate homeostasis, differentiation, and development. T3Rs are synthesized as multiple isoforms that display tissue-specific expression patterns and distinct transcriptional properties. Most T3R isoforms associate with coactivator proteins and mediate transcriptional activation only in the presence of thyroid hormone. The pituitary-specific T3Rβ-2 isoform departs from this general rule and is able to interact with p160 coactivators, and to mediate transcriptional activation in both the absence and presence of hormone. We report here that this hormone-independent activation is mediated by contacts between the unique N terminus of T3Rβ-2 and an internal interaction domain in the SRC-1 (steroid receptor coactivator-1) and GRIP-1 (glucocorticoid receptor interacting protein 1) coactivators. These hormone-independent contacts between T3Rβ-2 and the p160 coactivators are distinct in sequence and function from the LXXLL motifs that mediate hormone-dependent transcriptional activation and resemble instead a mode of coactivator recruitment previously observed only for the steroid hormone receptors and only in the presence of steroid hormone. Our results suggest that the transcriptional properties of the different T3R isoforms represent a combinatorial mixture of repression, antirepression, and hormone-independent and hormone-dependent activation functions that operate in conjunction to determine the ultimate transcriptional outcome.

scholarly journals Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching.

1993 ◽  
Vol 13 (12) ◽  
pp. 7698-7707 ◽  
Author(s):  
J M Lehmann ◽  
X K Zhang ◽  
G Graupner ◽  
M O Lee ◽  
T Hermann ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptors ◽  
Cross Talk ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Retinoid X Receptor ◽  
Thyroid Hormone Receptors ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
X Receptors

Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.

scholarly journals Estrogen-Dependent Transactivation of Amphioxus Steroid Hormone Receptor via Both Estrogen and Androgen Response Elements

Endocrinology ◽  
2010 ◽  
Vol 151 (2) ◽  
pp. 639-648 ◽  
Author(s):  
Yoshinao Katsu ◽  
Kaoru Kubokawa ◽  
Hiroshi Urushitani ◽  
Taisen Iguchi
Keyword(s):  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Steroid Receptors ◽  
Steroid Hormone ◽  
Steroid Hormone Receptors ◽  
Female Reproductive System ◽  
Sex Steroid Hormone ◽  
Branchiostoma Belcheri ◽  
Experimental Approaches ◽  
Developmental Windows

Estrogens are necessary for ovarian differentiation during critical developmental windows in most vertebrates and promote the growth and differentiation of the adult female reproductive system. Estrogen actions are largely mediated through the estrogen receptors (ERs), which are ligand-activated transcription factors. To understand the molecular evolution of sex steroid hormone receptors, we isolated cDNAs encoding two steroid receptors from Japanese amphioxus, Branchiostoma belcheri: an ER ortholog and a ketosteroid receptor (SR) ortholog. Reporter gene assays revealed that the SR ortholog has molecular functions similar to those of the vertebrate ER. Surprisingly, the ER ortholog is an estrogen-insensitive repressor of SR-mediated transcription. Furthermore, we found that the SR ortholog can bind to both estrogen-responsive elements (EREs) and androgen-responsive elements (AREs) and mediates transcriptional activation by estrogens through both types of elements. Our findings suggest that the ancestral SR, but not ER, could bind estrone and induce the ERE- and ARE-dependent transactivation and that it gained the ability to be regulated by ketosteroid and recognize ARE specifically before jawless vertebrates split. These results highlight the importance of comparative experimental approaches for the evolutionary study of endocrine systems.

Formation of retinoid X receptor homodimers leads to repression of T3 response: hormonal cross talk by ligand-induced squelching

1993 ◽  
Vol 13 (12) ◽  
pp. 7698-7707
Author(s):  
J M Lehmann ◽  
X K Zhang ◽  
G Graupner ◽  
M O Lee ◽  
T Hermann ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptors ◽  
Cross Talk ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Retinoid X Receptor ◽  
Thyroid Hormone Receptors ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
X Receptors

Thyroid hormone receptors (TRs) form heterodimers with retinoid X receptors (RXRs). Heterodimerization is required for efficient TR DNA binding to most response elements and transcriptional activation by thyroid hormone. RXRs also function as auxiliary proteins for several other receptors. In addition, RXR alpha can be induced by specific ligands to form homodimers. Here we report that RXR-specific retinoids that induce RXR homodimers are effective repressors of the T3 response. We provide evidence that this repression by RXR-specific ligands occurs by sequestering of RXR from TR-RXR heterodimers into RXR homodimers. This ligand-induced squelching may represent an important mechanism by which RXR-specific retinoids and 9-cis retinoic acid mediate hormonal cross talk among a subfamily of nuclear receptors activated by structurally unrelated ligands.

Sign in / Sign up

Export Citation Format

Share Document