ArticleEndocrinology2009
In vivo interaction of steroid receptor coactivator (SRC)-1 and the activation function-2 domain of the thyroid hormone receptor (TR) beta in TRbeta E457A knock-in and SRC-1 knockout mice.
Article in Endocrinology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Transcriptional Cofactors for Thyroid Hormone Receptors.Endocrinology · 2025Review
- Molecular Dynamic Simulation To Reveal the Mechanism Underlying MGL-3196 Resistance to Thyroxine Receptor Beta.ACS omega · 2024Article
- Obesity Due to Steroid Receptor Coactivator-1 Deficiency Is Associated With Endocrine and Metabolic Abnormalities.The Journal of clinical endocrinology and metabolism · 2022Article
- Thyroid disrupting chemicals and developmental neurotoxicity - New tools and approaches to evaluate hormone action.Molecular and cellular endocrinology · 2020Review
- Nuclear Receptor Coactivators (NCOAs) and Corepressors (NCORs) in the Brain.Endocrinology · 2020Review
- Article
- Thyroid hormone receptors and resistance to thyroid hormone disorders.Nature reviews. Endocrinology · 2014Review
- Thyroid hormone signaling in vivo requires a balance between coactivators and corepressors.Molecular and cellular biology · 2014Article
- Thyroid hormone regulation of metabolism.Physiological reviews · 2014Review
- Novel mechanism of positive versus negative regulation by thyroid hormone receptor β1 (TRβ1) identified by genome-wide profiling of binding sites in mouse liver.The Journal of biological chemistry · 2014Article
- Synthesis and evaluation of methylsulfonylnitrobenzamides (MSNBAs) as inhibitors of the thyroid hormone receptor-coactivator interaction.Bioorganic & medicinal chemistry letters · 2013Article
- Mechanisms of thyroid hormone action.The Journal of clinical investigation · 2012Review
- Synthesis and evaluation of sulfonylnitrophenylthiazoles (SNPTs) as thyroid hormone receptor-coactivator interaction inhibitors.Journal of medicinal chemistry · 2012Article
- Variable clinical presentation and outcome in pediatric patients with resistance to thyroid hormone (RTH).Endocrine · 2012Article
- Methylsulfonylnitrobenzoates, a new class of irreversible inhibitors of the interaction of the thyroid hormone receptor and its obligate coactivators that functionally antagonizes thyroid hormone.The Journal of biological chemistry · 2011Article
- The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.Molecular endocrinology (Baltimore, Md.) · 2011Article
- Article
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
The activation function-2 (AF-2) domain of the thyroid hormone (TH) receptor (TR)-beta is a TH-dependent binding site for nuclear coactivators (NCoA), which modulate TH-dependent gene transcription. In contrast, the putative AF-1 domain is a TH-independent region interacting with NCoA. We determined the specificity of the AF-2 domain and NCoA interaction by evaluating thyroid function in mice with combined disruption of the AF-2 domain in TRbeta, due to a point mutation (E457A), and deletion of one of the NCoAs, steroid receptor coactivator (SRC)-1. The E457A mutation was chosen because it abolishes NCoA recruitment in vitro while preserving normal TH binding and corepressor interactions resulting in resistance to TH. At baseline, disruption of SRC-1 in the homozygous knock-in (TRbeta(E457A/E457A)) mice worsened the degree of resistance to TH, resulting in increased serum T(4) and TSH. During TH deprivation, disruption of AF-2 and SRC-1 resulted in a TSH rise 50% of what was seen when AF-2 alone was removed, suggesting that SRC-1 was interacting outside of the AF-2 domain. Therefore, 1) during TH deprivation, SRC-1 is necessary for activating the hypothalamic-pituitary-thyroid axis; 2) ligand-dependent repression of TSH requires an intact AF-2; and 3) SRC-1 may interact with the another region of the TRbeta or the TRalpha to regulate TH action in the pituitary. This report demonstrates the dual interaction of NCoA in vivo: the TH-independent up-regulation possibly through another domain and TH-dependent down-regulation through the AF-2 domain.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.