ArticleBiochimica et biophysica acta
Activation of testicular orphan receptor 4 by fatty acids.
Article in Biochimica et biophysica acta. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Coregulatory Networks Remodel the Disease-Specific Functions of Orphan Nuclear Receptor TR4.Cells · 2026Review
- Review
- Structures of human TR4LBD-JAZF1 and TR4DBD-DNA complexes reveal the molecular basis of transcriptional regulation.Nucleic acids research · 2023Article
- Identification of Small-Molecule Regulators of Testicular Receptor 4 via a Drug Repurposing Screening.ACS omega · 2020Article
- TR4 nuclear receptor enhances prostate cancer initiation via altering the stem cell population and EMT signals in the PPARG-deleted prostate cells.Oncoscience · 2015Article
- TR4 Nuclear Receptor Different Roles in Prostate Cancer Progression.Frontiers in endocrinology · 2015Review
- Fetal globin gene repressors as drug targets for molecular therapies to treat the β-globinopathies.Molecular and cellular biology · 2014Review
- Minireview: Pathophysiological roles of the TR4 nuclear receptor: lessons learned from mice lacking TR4.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Recent advances in the study of testicular nuclear receptor 4.Journal of Zhejiang University. Science. B · 2013Article
- Deficiency in TR4 nuclear receptor abrogates Gadd45a expression and increases cytotoxicity induced by ionizing radiation.Cellular & molecular biology letters · 2012Article
- Testicular nuclear receptor 4 (TR4) regulates UV light-induced responses via Cockayne syndrome B protein-mediated transcription-coupled DNA repair.The Journal of biological chemistry · 2011Article
- Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells.Molecular and cellular biology · 2011Article
- Increased acetylation in the DNA-binding domain of TR4 nuclear receptor by the coregulator ARA55 leads to suppression of TR4 transactivation.The Journal of biological chemistry · 2011Article
- Metformin inhibits nuclear receptor TR4-mediated hepatic stearoyl-CoA desaturase 1 gene expression with altered insulin sensitivity.Diabetes · 2011Article
- Article
- Genome-wide binding of the orphan nuclear receptor TR4 suggests its general role in fundamental biological processes.BMC genomics · 2010Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Nuclear receptors can be activated by chemicals, metabolites, hormones or environmental compounds to regulate gene expression. Bioassay-guided screening of mouse tissue extracts found that natural fatty acids of a certain carbon length and level of unsaturation could activate the mouse orphan nuclear receptor, testicular orphan receptor 4 (TR4). Subsequent experiments focused on gamma-linoleic acid, a compound identified during screening of mouse tissues that exerts regulatory activity in TR4 transactivation assays. gamma-linoleic acid positively modulates TR4 activity to promote the expression of downstream genes such as apolipoprotein E (ApoE) and phosphoenolpyruvate carboxykinase, and to activate a reporter carrying direct repeat 1 from the ApoE promoter. It also induced the interaction of TR4 with transcription coregulators such as RIP140 and PCAF. Comparisons of transactivation by TR4 and the metabolism-related peroxisome proliferator-activated nuclear receptors indicate that gamma-linoleic acid regulation is specific to TR4. The data suggest that TR4 might exert its physiological function by sensing certain lipids. Identifying these compounds could be useful for examining the physiological pathways in which TR4 and its target genes are involved.
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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.