Evidence map›Paper›PMID 8990194›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America1997

A natural transactivation mutation in the thyroid hormone beta receptor: impaired interaction with putative transcriptional mediators.

T N Collingwood, O Rajanayagam, M Adams, R Wagner, V Cavaillès, E Kalkhoven, C Matthews, E Nystrom, K Stenlof, G Lindstedt and 4 more

Open access · greenAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 1997. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed, 1 pooled it
10.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 1 synthesis or guideline pooled it, 117 citations in OpenAlex.

  1. Guideline
  2. Review
  3. Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. A novel 1297-1304delGCCTGCCA mutation in the exon 10 of the thyroid hormone receptor β gene causes resistance to thyroid hormone.Molecular diagnosis : a journal devoted to the understanding of human disease through the clinical application of molecular biology · 2004
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 2 countries.

T N CollingwoodDepartment of Medicine, University of Cambridge, Addenbrooke's Hospital, United Kingdom.
O Rajanayagam
M Adams
R Wagner
V Cavaillès
E Kalkhoven
C Matthews
E Nystrom
K Stenlof
G Lindstedt
L Tisell
R J Fletterick
M G Parker
V K Chatterjee
The Honourable Society of Lincoln's Inn · GBUniversity of Gothenburg · SEAddenbrooke's Hospital · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

The syndrome of resistance to thyroid hormone is characterized by elevated serum free thyroid hormones, failure to suppress pituitary thyrotropin secretion, and variable peripheral refractoriness to hormone action. Here we describe a novel leucine to valine mutation in codon 454 (L454V) of the thyroid hormone beta receptor (TR beta) in this disorder, resulting in a mutant receptor with unusual functional properties. Although the mutant protein binds ligand comparably to wild-type receptor and forms homo- and heterodimers on direct repeat, everted repeat, or palindromic thyroid response elements, its ability to activate transcription via these elements is markedly impaired. The hydrophobic leucine residue lies within an amphipathic alpha-helix at the carboxyl terminus of TR beta and the position of the homologous residue in the crystal structure of TR alpha indicates that its side chain is solvent-exposed and might interact with other proteins. We find that two putative transcriptional mediators (RIP140 and SRC-1) exhibit hormone-dependent association with wild-type TR. In comparison, the interaction of this natural mutant (L454V) and artificial mutants (L454A, E457A) with RIP140 and SRC-1 is markedly reduced. Furthermore, coexpression of SRC-1 is able to restore the transcriptional activity of the L454V mutant receptor, indicating that the interaction of this residue with accessory proteins is critical for transcriptional activation. Finally, the occurrence of the L454V mutation in resistance to thyroid hormone, together with impaired negative regulation of the thyroid-stimulating hormone alpha promoter by this mutant, suggests that the amphipathic alpha-helix also mediates hormone-dependent transcriptional inhibition, perhaps via interaction with these or other accessory factors.

Indexed as

MutationTranscriptional ActivationAdaptor Proteins, Signal TransducingAdultBinding SitesDimerizationDNA-Binding ProteinsGenes, ReporterHistone AcetyltransferasesHumansLeucineModels, MolecularNuclear ProteinsNuclear Receptor Coactivator 1Nuclear Receptor Interacting Protein 1Protein BindingAdaptor Proteins, Signal TransducingDNA-Binding ProteinsHistone AcetyltransferasesLeucineNCOA1 protein, humanNRIP1 protein, humanNuclear ProteinsNuclear Receptor Coactivator 1Nuclear Receptor Interacting Protein 1Receptors, Thyroid HormoneRecombinant ProteinsThyroid HormonesTranscription FactorsValine

Identifiers

PMID8990194
PMCPMC19304
OpenAlexW2163188040

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.