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A Novel Cytoplasmic Adaptor for Retinoic Acid Receptor (RAR) and Thyroid Receptor Functions as a Derepressor of RAR in the Absence of Retinoic Acid*
Open accessAbstract
In most mammalian cells, the retinoic acid receptor (RAR) is nuclear rather than cytoplasmic, regardless of its cognate ligand, retinoic acid (RA). In testis Sertoli cells, however, RAR is retained in the cytoplasm and moves to the nucleus only when RA is supplied. This led us to identify a protein that regulates the translocation of RAR. From yeast two-hybrid screening, we identified a novel RAR-interacting protein called CART1 (cytoplasmic adaptor for RAR and TR). Systematic interaction assays using deletion mutants showed that the C-terminal CoRNR box of CART1 was responsible for the interaction with the NCoR binding region of RAR and TR. Such interaction was impaired in the presence of ligand RA, as further determined by GST pulldown assays in vitro and immunoprecipitation assays in vivo. Fluorescence microscopy showed that unliganded RAR was captured by CART1 in the cytoplasm, whereas liganded RAR was liberated and moved to the nucleus. Overexpression of CART1 blocked the transcriptional repressing activity of unliganded apoRAR, mediated by corepressor NCoR in the nucleus. CART1 siRNA treatment in a mouse Sertoli cell line, TM4, allowed RAR to move to the nucleus and blocked the derepressing function of CART1, suggesting that CART1 might be a cytoplasmic, testis-specific derepressor of RAR.
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“In Sertoli cells and hepatic stellate cells, a cytosolic localization of RAR ␣ has been also observed upon interaction with the cytoplasmic adaptor for RAR and TR (CART1) protein or with cytoskeleton proteins that sequester the receptor out of nuclei ( 154, 155 ).”
From Vitamin A and retinoid signaling: genomic and nongenomic effects (2013) · cites this paper as [154]
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Cited by
Sorted by citations
Vitamin A and retinoid signaling: genomic and nongenomic effects
Al Tanoury, Z., Piskunov, A., & Rochette-Egly, C. (2013) · Journal of Lipid Research · doi:10.1194/jlr.r030833 · Cited by 408
Metadata
- Authors
- Park, U.-H., Kim, E.-J., & Um, S.-J.
- Affiliations
- Sejong University (KR)
- Corresponding author
- Um, Soo-Jong
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 285
- Issue
- 44
- Pages
- 34269-34278
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2962525
- OpenAlex
- W2058958130
- Cited by
- 15
- References
- 1
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 4 · 2016: 1 · 2013: 2 · 2012: 1
- FWCI
- 0.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Receptors and Signaling
- Keywords
- retinoic acid receptor, thyroid hormone receptor, retinoic acid, nuclear translocation, transcriptional derepression, Sertoli cells, testis-specific proteins, protein-protein interaction
- MeSH terms
- Animals, Cell Nucleus, Cytoplasm, Gene Expression Regulation, Humans, Male, Microscopy, Fluorescence, Receptors, Thyroid Hormone, Sertoli Cells, Testis, Transcription Factors, Tretinoin, Receptors, Retinoic Acid, Two-Hybrid System Techniques, NIH 3T3 Cells, Mice
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- Park, U.-H., Kim, E.-J., & Um, S.-J. (2010). A Novel Cytoplasmic Adaptor for Retinoic Acid Receptor (RAR) and Thyroid Receptor Functions as a Derepressor of RAR in the Absence of Retinoic Acid*. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110.143008