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.

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 Activation and repression by nuclear hormone receptors: hormone modulates an equilibrium between active and repressive states.

1996 ◽  
Vol 16 (7) ◽  
pp. 3807-3813 ◽  
Author(s):  
I G Schulman ◽  
H Juguilon ◽  
R M Evans
Keyword(s):  
Thyroid Hormone ◽  
Nuclear Receptors ◽  
Hormone Receptors ◽  
Retinoid X Receptor ◽  
Thyroid Hormone Receptors ◽  
Hormone Binding ◽  
Vitamin D Receptors ◽  
The Common ◽  
Hormonal Activation ◽  
Hormone Binding Domain

Transactivation-defective retinoid X and thyroid hormone receptors have been used to examine mechanisms of hormonal activation. Activation and repression of transcription by retinoid X and thyroid hormone receptors are shown to be mediated by physically distinct and functionally independent regions of the hormone binding domain. Nevertheless, the ability of receptors to respond to hormone requires communication between both functional domains. Deletion of the hormone-dependent transactivation function of the retinoid X receptor, the common subunit of heterodimeric nuclear receptors, significantly impairs hormone-dependent transcription by retinoic acid, thyroid hormone, and vitamin D receptors. The results indicate that receptors do not exist in static off and on conformations but that hormone alters an equilibrium between inactive and active states.

scholarly journals Widely spaced, directly repeated PuGGTCA elements act as promiscuous enhancers for different classes of nuclear receptors.

1995 ◽  
Vol 15 (11) ◽  
pp. 5858-5867 ◽  
Author(s):  
S Kato ◽  
H Sasaki ◽  
M Suzawa ◽  
S Masushige ◽  
L Tora ◽  
...  
Keyword(s):  
Vitamin D ◽  
Nuclear Receptors ◽  
Response Element ◽  
Binding Motifs ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
Cis Acting ◽  
X Receptors ◽  
Receptor Cross Talk ◽  
Site Recognition

We describe here a novel class of cis-acting response elements for retinoid, vitamin D, and estrogen receptors which are widely spaced (10 to 200 bp) direct repeats (DRs) of the canonical 5'-AGGTCA half-site recognition motif (DR10 to DR200). In contrast to the specificity previously observed with shortly spaced DRs (DR1 to DR5), the different receptors bind promiscuously to these novel elements to activate transcription in the presence of retinoic acid (RA), vitamin D, or estrogen. The greatest RA-dependent transactivation, seen with DR15, was similar to that observed with the canonical DR5. Both RA receptors and retinoid X receptors contribute to transactivation through widely spaced DR elements. With the estrogen receptor, DR15 was one-third as efficient as the classical palindromic response element. A further increase of spacer lengths progressively decreased the efficiency of transactivation. No transactivation was seen with widely spaced DRs when the thyroid and retinoid X receptors were coexpressed in the presence of their ligands. The progesterone receptor was also unable to transactivate through a DR10 element composed of its cognate binding motifs. These results considerably extend the response element repertoire of nuclear receptors and suggest the existence of promiscuous transcriptional regulation through common response elements, as well as the possibility of receptor "cross-talk."

The function of retinoid X receptors on negative thyroid hormone response elements

1997 ◽  
Vol 128 (1-2) ◽  
pp. 85-96 ◽  
Author(s):  
Teiji Takeda ◽  
Takeshi Nagasawa ◽  
Takahide Miyamoto ◽  
Kiyoshi Hashizume ◽  
Leslie J DeGroot
Keyword(s):  
Thyroid Hormone ◽  
Hormone Response ◽  
Retinoid X Receptors ◽  
Response Elements ◽  
Hormone Response Elements ◽  
X Receptors
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