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dc.contributor.authorMartin, Perrine J.
dc.contributor.authorDelmotte, Marie-Helene
dc.contributor.authorFormstecher, Pierre
dc.contributor.authorLefebvre, Philippe
dc.date2022-08-11T08:09:40.000
dc.date.accessioned2022-08-23T16:39:29Z
dc.date.available2022-08-23T16:39:29Z
dc.date.issued2003-09-06
dc.date.submitted2012-03-22
dc.identifier.citationNucl Recept. 2003 Sep 6;1(1):6. <a href="http://dx.doi.org/10.1186/1478-1336-1-6" target="_blank">Link to article on publisher's site</a> 2003 Martin et al; licensee BioMed Central Ltd.
dc.identifier.issn1478-1336 (Linking)
dc.identifier.doi10.1186/1478-1336-1-6
dc.identifier.pmid14521715
dc.identifier.pmid14521715
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39481
dc.description.abstractBACKGROUND: 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=14521715&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1186/1478-1336-1-6
dc.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.
dc.subjectKruppel-Like Transcription Factors
dc.subjectReceptors, Retinoic Acid
dc.subjectBiochemistry, Biophysics, and Structural Biology
dc.subjectGenetics and Genomics
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titlePLZF is a negative regulator of retinoic acid receptor transcriptional activity
dc.typeJournal Article
dc.source.journaltitleNuclear receptor
dc.source.volume1
dc.source.issue1
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3276&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2277
dc.identifier.contextkey2691116
refterms.dateFOA2022-08-23T16:39:29Z
html.description.abstract<p>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.</p> <p>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.</p> <p>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.</p>
dc.identifier.submissionpathoapubs/2277
dc.contributor.departmentDepartment of Biochemistry and Molecular Biology
dc.source.pages6


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