Abstract
Thyroid hormone receptors (T3Rs) both repress and activate gene transcription by interacting with auxiliary factors denoted corepressors and coactivators. Resistance to thyroid hormone (RTH) syndrome in humans is manifested as a failure to respond properly to elevated circulating thyroid hormone. RTH syndrome has been mapped to T3Rβ mutations that alter the transcriptional properties of the receptor, resulting in a dominant negative phenotype. We report here a characterization of a series of RTH mutant T3Rs that exhibit unusual interactions with corepressor. Two mutations in receptor helix 11 (Δ430, Δ432) greatly enhance the ability of the mutant receptors to bind to corepressor. A distinct mutation, V264D, in an 'omega loop' region of the receptor, impairs corepressor release but does not fully eliminate the ability to recruit coactivator. These mutations reveal novel determinants that regulate the interaction of the T3R with important ancillary cofactors, and that are disrupted in a human endocrine disease. (C) 2000 Elsevier Science Ireland Ltd.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 109-124 |
| Number of pages | 16 |
| Journal | Molecular and Cellular Endocrinology |
| Volume | 159 |
| Issue number | 1-2 |
| DOIs | |
| State | Published - Jan 25 2000 |
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Keywords
- Corepressor
- RTH syndrome
- SMRT
- Thyroid hormone receptor
ASJC Scopus subject areas
- Endocrinology
- Endocrinology, Diabetes and Metabolism
Cite this
Resistance to thyroid hormone (RTH) syndrome reveals novel determinants regulating interaction of T3 receptor with corepressor. / Privalsky, Martin L.; Yoh, Sunnie M.
In: Molecular and Cellular Endocrinology, Vol. 159, No. 1-2, 25.01.2000, p. 109-124.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Resistance to thyroid hormone (RTH) syndrome reveals novel determinants regulating interaction of T3 receptor with corepressor
AU - Privalsky, Martin L.
AU - Yoh, Sunnie M.
PY - 2000/1/25
Y1 - 2000/1/25
N2 - Thyroid hormone receptors (T3Rs) both repress and activate gene transcription by interacting with auxiliary factors denoted corepressors and coactivators. Resistance to thyroid hormone (RTH) syndrome in humans is manifested as a failure to respond properly to elevated circulating thyroid hormone. RTH syndrome has been mapped to T3Rβ mutations that alter the transcriptional properties of the receptor, resulting in a dominant negative phenotype. We report here a characterization of a series of RTH mutant T3Rs that exhibit unusual interactions with corepressor. Two mutations in receptor helix 11 (Δ430, Δ432) greatly enhance the ability of the mutant receptors to bind to corepressor. A distinct mutation, V264D, in an 'omega loop' region of the receptor, impairs corepressor release but does not fully eliminate the ability to recruit coactivator. These mutations reveal novel determinants that regulate the interaction of the T3R with important ancillary cofactors, and that are disrupted in a human endocrine disease. (C) 2000 Elsevier Science Ireland Ltd.
AB - Thyroid hormone receptors (T3Rs) both repress and activate gene transcription by interacting with auxiliary factors denoted corepressors and coactivators. Resistance to thyroid hormone (RTH) syndrome in humans is manifested as a failure to respond properly to elevated circulating thyroid hormone. RTH syndrome has been mapped to T3Rβ mutations that alter the transcriptional properties of the receptor, resulting in a dominant negative phenotype. We report here a characterization of a series of RTH mutant T3Rs that exhibit unusual interactions with corepressor. Two mutations in receptor helix 11 (Δ430, Δ432) greatly enhance the ability of the mutant receptors to bind to corepressor. A distinct mutation, V264D, in an 'omega loop' region of the receptor, impairs corepressor release but does not fully eliminate the ability to recruit coactivator. These mutations reveal novel determinants that regulate the interaction of the T3R with important ancillary cofactors, and that are disrupted in a human endocrine disease. (C) 2000 Elsevier Science Ireland Ltd.
KW - Corepressor
KW - RTH syndrome
KW - SMRT
KW - Thyroid hormone receptor
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UR - http://www.scopus.com/inward/citedby.url?scp=0033969578&partnerID=8YFLogxK
U2 - 10.1016/S0303-7207(99)00201-4
DO - 10.1016/S0303-7207(99)00201-4
M3 - Article
C2 - 10687857
AN - SCOPUS:0033969578
VL - 159
SP - 109
EP - 124
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
SN - 0303-7207
IS - 1-2
ER -