NDLI: A Novel Cytoplasmic Adaptor for Retinoic Acid Receptor (RAR) and Thyroid Receptor Functions as a Derepressor of RAR in the Absence of Retinoic Acid

Content Provider	Journal of Biological Chemistry (JBC)
Author	Park, Ui-Hyun Kim, Eun-Joo Um, Soo-Jong
Abstract	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.
Related Links	http://www.jbc.org/content/285/44/34269.abstract
Ending Page	34278
Starting Page	34269
Page Count	10
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	44
Volume Number	285
DOI	10.1074/jbc.M110.143008
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2010-10-29
Access Restriction	Open
Subject Keyword	Gene Regulation Hormone Receptors Protein Translocation Protein-Protein Interactions Repressor Protein Cytoplasmic Retention NCoR RAR Sertoli Cells Derepressor Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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