ArticlePloS one2010
The "Phantom Effect" of the Rexinoid LG100754: structural and functional insights.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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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.
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Who cites it
35 citing papers in PubMed, 73 citations in OpenAlex.
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- Synthetic Retinoids for the Modulation of Genomic and Nongenomic Processes in Neurodegenerative Diseases.ACS omega · 2025Article
- Simple Fluorescence Labeling Method Enables Detection of Intracellular Distribution and Expression Level of Retinoid X Receptors.ACS medicinal chemistry letters · 2024Article
- Unveiling the Mechanism of Retinoic Acid Therapy for Cutaneous Warts: Insights from Multi-Omics Integration.Clinical, cosmetic and investigational dermatology · 2024Article
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- Increased Molecular Flexibility Widens the Gap betweenACS medicinal chemistry letters · 2022Article
- Protection against influenza-induced Acute Lung Injury (ALI) by enhanced induction of M2a macrophages: possible role of PPARγ/RXR ligands in IL-4-induced M2a macrophage differentiation.Frontiers in immunology · 2022Article
- Rexinoids Modulate Effector T Cell Expression of Mucosal Homing Markers CCR9 and α4β7 Integrin and Direct Their MigrationFrontiers in immunology · 2022Article
- The effect of S427F mutation on RXRα activity depends on its dimeric partner.Chemical science · 2021Article
- New Approaches to Assess Mechanisms of Action of Selective Vitamin D Analogues.International journal of molecular sciences · 2021Review
- Creation of Fluorescent RXR Antagonists Based on CBTF-EE and Application to a Fluorescence Polarization Binding Assay.ACS medicinal chemistry letters · 2021Article
- Synthesis and biological evaluation of (3/4-(pyrimidin-2-ylamino)benzoyl)-based hydrazine-1-carboxamide/carbothioamide derivatives as novel RXRα antagonists.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Comprehensive Set of Tertiary Complex Structures and Palmitic Acid Binding Provide Molecular Insights into Ligand Design for RXR Isoforms.International journal of molecular sciences · 2020Article
- Regulation of RXR-RAR Heterodimers by RXR- and RAR-Specific Ligands and Their Combinations.Cells · 2019Article
- Mediation of antiinflammatory effects of Rg3-enriched red ginseng extract from Korean Red Ginseng via retinoid X receptor α-peroxisome-proliferating receptor γ nuclear receptors.Journal of ginseng research · 2019Article
- Retinoid X Receptor Antagonists.International journal of molecular sciences · 2018Review
- Non-genomic effects of nuclear receptors: insights from the anucleate platelet.Cardiovascular research · 2018Review
- Overview of the structure-based non-genomic effects of the nuclear receptor RXRα.Cellular & molecular biology letters · 2018Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinoic acid receptors (RARs) and Retinoid X nuclear receptors (RXRs) are ligand-dependent transcriptional modulators that execute their biological action through the generation of functional heterodimers. RXR acts as an obligate dimer partner in many signalling pathways, gene regulation by rexinoids depending on the liganded state of the specific heterodimeric partner. To address the question of the effect of rexinoid antagonists on RAR/RXR function, we solved the crystal structure of the heterodimer formed by the ligand binding domain (LBD) of the RARα bound to its natural agonist ligand (all-trans retinoic acid, atRA) and RXRα bound to a rexinoid antagonist (LG100754). We observed that RARα exhibits the canonical agonist conformation and RXRα an antagonist one with the C-terminal H12 flipping out to the solvent. Examination of the protein-LG100754 interactions reveals that its propoxy group sterically prevents the H12 associating with the LBD, without affecting the dimerization or the active conformation of RAR. Although LG100754 has been reported to act as a 'phantom ligand' activating RAR in a cellular context, our structural data and biochemical assays demonstrate that LG100754 mediates its effect as a full RXR antagonist. Finally we show that the 'phantom ligand effect' of the LG100754 is due to a direct binding of the ligand to RAR that stabilizes coactivator interactions thus accounting for the observed transcriptional activation of RAR/RXR.
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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.