Evidence mapPaperPMID 41036627Full record

ArticleNucleic acids research2025

New structural insights into the control of the retinoic acid receptors RAR/RXR by DNA, ligands, and transcriptional coregulators.

Izabella Tambones, Amin Sagar, Pavla Vankova, Dmitry Loginov, Coralie Carivenc, Natacha Rochel, William Bourguet, Petr Man, Pau Bernadó, Albane le Maire

Abstract read
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
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

4 citing papers in PubMed.

  1. Triorganotin compounds as emerging nuclear retinoid X receptor ligands and their implications in cancer.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
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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

10 authors.

Izabella TambonesCenter for Structural Biology (CBS), University of Montpellier, CNRS UMR 5048, INSERM U 1054, Montpellier 34090, France.ORCID 0000-0002-4073-9227
Amin SagarCenter for Structural Biology (CBS), University of Montpellier, CNRS UMR 5048, INSERM U 1054, Montpellier 34090, France.
Pavla VankovaInstitute of Biotechnology of the Czech Academy of Sciences, Division BioCeV, Prumyslova 595, Vestec 25250, Czech Republic.
Dmitry LoginovInstitute of Microbiology of the Czech Academy of Sciences, Division BioCeV, Prumyslova 595, Vestec 25250, Czech Republic.
Coralie CarivencCenter for Structural Biology (CBS), University of Montpellier, CNRS UMR 5048, INSERM U 1054, Montpellier 34090, France.
Natacha RochelInstitute of Genetics and Molecular and Cellular Biology, University of Strasbourg, CNRS UMR7104, INSERM U 1258, Illkirch-Graffenstaden 67404, France.ORCID 0000-0002-3573-5889
William BourguetCenter for Structural Biology (CBS), University of Montpellier, CNRS UMR 5048, INSERM U 1054, Montpellier 34090, France.
Petr ManInstitute of Microbiology of the Czech Academy of Sciences, Division BioCeV, Prumyslova 595, Vestec 25250, Czech Republic.
Pau BernadóCenter for Structural Biology (CBS), University of Montpellier, CNRS UMR 5048, INSERM U 1054, Montpellier 34090, France.
Albane le MaireCenter for Structural Biology (CBS), University of Montpellier, CNRS UMR 5048, INSERM U 1054, Montpellier 34090, France.ORCID 0000-0003-3336-2158

Funding

ANR ANR-21-CE11-0005-01ANR APPID: 2524BioCeV CMS PID: 22 036CMS BIOCEV CZ.02.01.01/00/23_015/0008175CMS BIOCEV MEYS LM2023042EPIC-XS EPIC-XS-0000264French National Research Agency ANR-10-INBS-05FRISBI ANR-10-INBS-0005-02GENCI 2022-A0130713813GENCI 2022-AD010713745GRALGrenoble Instruct-ERIC UAR 3518 CNRS-CEA-UGA-EMBLInstitut National du CancerINTER-MICRO CZ.02.01.01/00/22_008/0004597
6 · The paper itself

Abstract

Retinoic acid receptors (RARs) are ligand-dependent transcription factors essential for various biological processes, including embryogenesis, differentiation, and apoptosis. RARs function as heterodimers with retinoid X receptors (RXRs) and regulate gene expression via retinoic acid response elements (RAREs). Their transcriptional activity is modulated by coregulators, with corepressors maintaining repression in the absence of ligand and coactivators enabling transcription upon ligand binding. Structural studies reveal that DNA binding induces conformational changes affecting coregulator interactions. However, the precise structural organization of RAR/RXR-coregulator complexes and the allosteric influence of DNA on receptor function remain incompletely understood. Our study presents an integrative analysis of the RAR/RXR heterodimer bound to four distinct and relevant RAREs (DR0, DR1, DR5, and IR0) in complex with either a corepressor (NCoR) or a coactivator (TIF-2) nuclear receptor interaction domain. By combining small-angle X-ray scattering, hydrogen/deuterium exchange mass spectrometry, and molecular dynamics simulations, we revealed that the heterodimer adopts distinct conformations depending on the DNA sequence, influencing interdomain distances and receptor interactions. Additionally, we uncovered the dynamic interplay between ligand, DNA, and coregulator binding. This study provides new insights into the structural features of coregulator proteins and highlights the allosteric influence of RAREs on receptor function.

Indexed as

DNAReceptors, Retinoic AcidRetinoid X ReceptorsHumansLigandsMolecular Dynamics SimulationNuclear Receptor Coactivator 2Nuclear Receptor Co-Repressor 1Nuclear Receptor Co-Repressor 2Protein BindingResponse ElementsScattering, Small AngleDNALigandsNCOA2 protein, humanNCOR2 protein, humanNuclear Receptor Coactivator 2Nuclear Receptor Co-Repressor 1Nuclear Receptor Co-Repressor 2Receptors, Retinoic AcidRetinoid X Receptors

Identifiers

PMID41036627
PMCPMC12489474

What Socratic holds

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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 Socratic graph.