ArticleThe EMBO journal1998
A role for helix 3 of the TRbeta ligand-binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone.
Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 144 citations in OpenAlex.
- Novel Thyroid Hormone Receptor β Gene Variant (F245L) Causing Mild Resistance to Thyroid Hormone.JCEM case reports · 2025Article
- Structure-Guided Approach to Relieving Transcriptional Repression in Resistance to Thyroid Hormone α.Molecular and cellular biology · 2022Article
- Tissue sensitivity to thyroid hormones may change over time.European thyroid journal · 2022Article
- Clinical Consequences of Variable Results in the Measurement of Free Thyroid Hormones: Unusual Presentation of a Family with a Novel Variant in theEuropean thyroid journal · 2021Article
- Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals.International journal of molecular sciences · 2020Review
- Mutational Landscape of Resistance to Thyroid Hormone Beta (RTHβ).Molecular diagnosis & therapy · 2019Review
- Assessing the clinical and molecular diagnosis of inherited forms of impaired sensitivity to thyroid hormone from a single tertiary center.Endocrine · 2018Article
- BRAFOncology letters · 2017Article
- Functional analyses of a novel missense and other mutations of the vitamin D receptor in association with alopecia.Scientific reports · 2017Article
- A clinician's guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms.Clinical diabetes and endocrinology · 2017Article
- Review
- A novel mutation of the THRB gene in a Japanese family with resistance to thyroid hormone.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2016Article
- Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease.Thyroid : official journal of the American Thyroid Association · 2013Article
- The syndromes of reduced sensitivity to thyroid hormone.Biochimica et biophysica acta · 2013Review
- Nuclear corepressors mediate the repression of phospholipase A2 group IIa gene transcription by thyroid hormone.The Journal of biological chemistry · 2013Article
- Multiple novel signals mediate thyroid hormone receptor nuclear import and export.The Journal of biological chemistry · 2012Article
- A two-day-old hyperthyroid neonate with thyroid hormone resistance born to a mother with well-controlled Graves' disease: a case report.Journal of medical case reports · 2012Article
- Homozygous thyroid hormone receptor β-gene mutations in resistance to thyroid hormone: three new cases and review of the literature.The Journal of clinical endocrinology and metabolism · 2012Review
- Genetic features of thyroid hormone receptors.Journal of genetics · 2012Review
- Thyroid hormone receptor mutations in cancer and resistance to thyroid hormone: perspective and prognosis.Journal of thyroid research · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 1 institution in 1 country.
Funding
Abstract
Resistance to thyroid hormone (RTH) has hitherto been associated with thyroid hormone beta receptor (TRbeta) mutations which cluster in two regions (alphaalpha 310-353 and alphaalpha 429-461) of the hormone-binding domain and closely approximate the ligand-binding cavity. Here, we describe a third cluster of RTH mutations extending from alphaalpha 234-282 which constitute a third boundary of the ligand pocket. One mutant, T277A, exhibits impaired transactivation which is disproportionate to its mildly reduced ligand affinity (Ka). T3-dependent recruitment of coactivators (SRC-1, ACTR) by mutant receptor-RXR heterodimers was reduced in comparison with wild-type. Cotransfection of SRC-1 restored transactivation by T277A. In the TRbeta crystal structure this helix 3 residue is surface-exposed and is in close proximity to residues L454 and E457 in helix 12 which are known to be critical for coactivator interaction, suggesting that they all constitute part of a receptor-coactivator interface. The transcriptional function of other mutants (A234T, R243W/Q, A268D, Delta276I, A279V, R282S) in this cluster correlated with their reduced Ka and they inhibited wild-type TRbeta action in a dominant negative manner. DNA binding, heterodimerization and corepressor recruitment were preserved in all mutants, signifying the importance of these attributes for dominant negative activity and correlating with the absence of natural mutations in regions bordering the third cluster which mediate these functions.
Indexed as
Identifiers
What OpenQuestion holds
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.