ArticleThe Journal of biological chemistry2011
The orphan nuclear receptor TR4 is a vitamin A-activated nuclear receptor.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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
48 citing papers in PubMed, 76 citations in OpenAlex.
- Coregulatory Networks Remodel the Disease-Specific Functions of Orphan Nuclear Receptor TR4.Cells · 2026Review
- Transcriptomic Profiling Identifies Key Genes and ERBB Signaling Pathway Associated with Aggressive Behavior in Muscovy Ducks (Animals : an open access journal from MDPI · 2026Article
- Review
- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
- PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.Science advances · 2024Article
- Review
- Review
- Cellular and micro-environmental responses influencing the antitumor activity of all-trans retinoic acid in breast cancer.Cell communication and signaling : CCS · 2024Review
- Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation.Nucleic acids research · 2023Article
- How does retinoic acid (RA) signaling pathway regulate spermatogenesis?Histology and histopathology · 2022Review
- Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs.Acta biochimica et biophysica Sinica · 2022Article
- TLX, an Orphan Nuclear Receptor With Emerging Roles in Physiology and Disease.Endocrinology · 2021Review
- Synthetic Retinoids as Potential Therapeutics in Prostate Cancer-An Update of the Last Decade of Research: A Review.International journal of molecular sciences · 2021Review
- Targeting the TR4 nuclear receptor with antagonist bexarotene can suppress the proopiomelanocortin signalling in AtT-20 cells.Journal of cellular and molecular medicine · 2021Article
- Identification of Small-Molecule Regulators of Testicular Receptor 4 via a Drug Repurposing Screening.ACS omega · 2020Article
- Strategies for developing pregnane X receptor antagonists: Implications from metabolism to cancer.Medicinal research reviews · 2020Review
- Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription.Cells · 2020Review
- Article
- Modulation of retinoid signaling: therapeutic opportunities in organ fibrosis and repair.Pharmacology & therapeutics · 2020Review
- Definition of functionally and structurally distinct repressive states in the nuclear receptor PPARγ.Nature communications · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Testicular receptors 2 and 4 (TR2/4) constitute a subgroup of orphan nuclear receptors that play important roles in spermatogenesis, lipid and lipoprotein regulation, and the development of the central nervous system. Currently, little is known about the structural features and the ligand regulation of these receptors. Here we report the crystal structure of the ligand-free TR4 ligand binding domain, which reveals an autorepressed conformation. The ligand binding pocket of TR4 is filled by the C-terminal half of helix 10, and the cofactor binding site is occupied by the AF-2 helix, thus preventing ligand-independent activation of the receptor. However, TR4 exhibits constitutive transcriptional activity on multiple promoters, which can be further potentiated by nuclear receptor coactivators. Mutations designed to disrupt cofactor binding, dimerization, or ligand binding substantially reduce the transcriptional activity of this receptor. Importantly, both retinol and retinoic acid are able to promote TR4 to recruit coactivators and to activate a TR4-regulated reporter. These findings demonstrate that TR4 is a ligand-regulated nuclear receptor and suggest that retinoids might have a much wider regulatory role via activation of orphan receptors such as TR4.
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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.