ArticleMolecular and cellular biology2003
Isotype-restricted corepressor recruitment: a constitutively closed helix 12 conformation in retinoic acid receptors beta and gamma interferes with corepressor recruitment and prevents transcriptional repression.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.Journal of molecular graphics & modelling · 2023Pooled it
- PML-driven sumoylation of PML::RARA-bound repressors drives hematopoietic progenitor immortalization.The Journal of experimental medicine · 2026Article
- Impaired retinoic acid receptor-γ signaling underlies a heritable form of urothelial keratinizing squamous metaplasia.HGG advances · 2026Article
- Antagonizing RARγ Drives Necroptosis of Cancer Stem Cells.International journal of molecular sciences · 2022Review
- RARG S427L attenuates the DNA repair response to doxorubicin in induced pluripotent stem cell-derived cardiomyocytes.Stem cell reports · 2022Article
- Trifarotene: A Current Review and Perspectives in Dermatology.Biomedicines · 2021Review
- Variation in RARG increases susceptibility to doxorubicin-induced cardiotoxicity in patient specific induced pluripotent stem cell-derived cardiomyocytes.Scientific reports · 2020Article
- The Pleiotropic Role of Retinoic Acid/Retinoic Acid Receptors Signaling: From Vitamin A Metabolism to Gene Rearrangements in Acute Promyelocytic Leukemia.International journal of molecular sciences · 2019Review
- Antagonizing Retinoic Acid Receptors Increases Myeloid Cell Production by Cultured Human Hematopoietic Stem Cells.Archivum immunologiae et therapiae experimentalis · 2017Article
- Retinoids and rexinoids in cancer prevention: from laboratory to clinic.Seminars in oncology · 2016Review
- Enhanced expression of retinoic acid receptor alpha (RARA) induces epithelial-to-mesenchymal transition and disruption of mammary acinar structures.Molecular oncology · 2015Article
- Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases.Journal of experimental neuroscience · 2015Review
- The ability of thyroid hormone receptors to sense t4 as an agonist depends on receptor isoform and on cellular cofactors.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Vitamin A and retinoid signaling: genomic and nongenomic effects.Journal of lipid research · 2013Review
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- Zebrafish retinoic acid receptors function as context-dependent transcriptional activators.Developmental biology · 2011Article
- Aberrant corepressor interactions implicated in PML-RAR(alpha) and PLZF-RAR(alpha) leukemogenesis reflect an altered recruitment and release of specific NCoR and SMRT splice variants.The Journal of biological chemistry · 2011Article
- Liganded RARalpha and RARgamma interact with but are repressed by TNIP1.Biochemical and biophysical research communications · 2009Article
- Thyroid hormone receptor mutations found in renal clear cell carcinomas alter corepressor release and reveal helix 12 as key determinant of corepressor specificity.Molecular endocrinology (Baltimore, Md.) · 2009Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Retinoic acid receptors (RARs) are ligand-regulated transcription factors that play multiple roles in vertebrate development and differentiation. RARs as a class are capable of both repressing and activating target gene expression. Transcriptional repression is mediated through the recruitment of corepressor proteins such as SMRT. Notably, vertebrates encode three major forms of RARs, alpha, beta, and gamma, and these distinct RAR isotypes differ in the ability to recruit a corepressor. RAR alpha strongly interacts with SMRT and can repress target gene transcription, whereas RAR beta and -gamma interact with SMRT only weakly and fail to repress. We report here the use of a genetic suppressor approach, based on a yeast two-hybrid interaction assay using Saccharomyces cerevisiae, for the isolation of RAR beta mutants that have gained the RAR alpha-like corepressor phenotype, i.e., a strong interaction with SMRT and the ability to repress gene expression in vertebrate cells. Analysis of these gain-of-function mutants indicates that the different corepressor interaction properties of RAR alpha, -beta and -gamma are determined by a gating mechanism through which amino acid differences in the helix 3 region of these receptors influence the position of the receptor C-terminal helix 12 domain. As a consequence, the RAR beta and RAR gamma receptors appear to adopt a constitutively closed helix 12 conformation in the absence of hormone that may approximate the conformation of RAR alpha when bound to hormone agonist. This closed helix 12 conformation in RAR beta and RAR gamma blocks corepressor binding, prevents repression, and permits significant levels of target gene activation even in the absence of hormone. We refer to this phenomenon as a "gate-latch" model of corepressor regulation.
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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.