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    PLZF is a negative regulator of retinoic acid receptor transcriptional activity

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    Martin_Nuclear_1478_1336_1_6.pdf
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    Authors
    Martin, Perrine J.
    Delmotte, Marie-Helene
    Formstecher, Pierre
    Lefebvre, Philippe
    UMass Chan Affiliations
    Department of Biochemistry and Molecular Biology
    Document Type
    Journal Article
    Publication Date
    2003-09-06
    Keywords
    Kruppel-Like Transcription Factors
    Receptors, Retinoic Acid
    Biochemistry, Biophysics, and Structural Biology
    Genetics and Genomics
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://dx.doi.org/10.1186/1478-1336-1-6
    Abstract
    BACKGROUND: Retinoic acid receptors (RARs) are ligand-regulated transcription factors controlling cellular proliferation and differentiation. Receptor-interacting proteins such as corepressors and coactivators play a crucial role in specifying the overall transcriptional activity of the receptor in response to ligand treatment. Little is known however on how receptor activity is controlled by intermediary factors which interact with RARs in a ligand-independent manner. RESULTS: We have identified the promyelocytic leukemia zinc finger protein (PLZF), a transcriptional corepressor, to be a RAR-interacting protein using the yeast two-hybrid assay. We confirmed this interaction by GST-pull down assays and show that the PLZF N-terminal zinc finger domain is necessary and sufficient for PLZF to bind RAR. The RAR ligand binding domain displayed the highest affinity for PLZF, but corepressor and coactivator binding interfaces did not contribute to PLZF recruitment. The interaction was ligand-independent and correlated to a decreased transcriptional activity of the RXR-RAR heterodimer upon overexpression of PLZF. A similar transcriptional interference could be observed with the estrogen receptor alpha and the glucocorticoid receptor. We further show that PLZF is likely to act by preventing RXR-RAR heterodimerization, both in-vitro and in intact cells. CONCLUSION: Thus RAR and PLZF interact physically and functionally. Intriguingly, these two transcription factors play a determining role in hematopoiesis and regionalization of the hindbrain and may, upon chromosomal translocation, form fusion proteins. Our observations therefore define a novel mechanism by which RARs activity may be controlled.
    Source
    Nucl Recept. 2003 Sep 6;1(1):6. Link to article on publisher's site 2003 Martin et al; licensee BioMed Central Ltd.
    DOI
    10.1186/1478-1336-1-6
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/39481
    PubMed ID
    14521715; 14521715
    Related Resources
    Link to Article in PubMed
    Rights
    © 2003 Martin et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
    ae974a485f413a2113503eed53cd6c53
    10.1186/1478-1336-1-6
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