title: Inactivation of the Nuclear Orphan Receptor COUP-TFII by Small Chemicals.
abstract: Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII/NR2F2) is an orphan member of the nuclear receptor family of transcription factors whose activities are modulated upon binding of small molecules into an hydrophobic ligand-binding pocket (LBP). Although the LBP of COUP-TFII is filled with aromatic amino-acid side chains, alternative modes of ligand binding could potentially lead to regulation of the orphan receptor. Here, we screened a synthetic and natural compound library in a yeast one-hybrid assay and identified 4-methoxynaphthol as an inhibitor of COUP-TFII. This synthetic inhibitor was able to counteract processes either positively or negatively regulated by COUP-TFII in different mammalian cell systems. Hence, we demonstrate that the true orphan receptor COUP-TFII can be targeted by small chemicals which could be used to study the physiological functions of COUP-TFII or to counteract detrimental COUP-TFII activities in various pathological conditions.
authors.affiliation: Université Rennes 1 , F-35042 Rennes, France.|UMR6290 CNRS, Team SP@RTE, Campus de Beaulieu, F-35042 Rennes, France.|SFR Biosit, UMS 3480 CNRS, US 018 INSERM, Campus de Villejean, F-35043 Rennes, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Le Guével
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: Frédérik
authors.initials: F
authors.lastname: Oger
authors.affiliation: B.S.R.C. "Alexander Fleming" , 34 Fleming Street, 16672 Vari, Greece.
authors.forename: Celia P
authors.initials: CP
authors.lastname: Martinez-Jimenez
authors.affiliation: Université Rennes 1 , F-35042 Rennes, France.|UMR6290 CNRS, Team SP@RTE, Campus de Beaulieu, F-35042 Rennes, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Bizot
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Gheeraert
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: François
authors.initials: F
authors.lastname: Firmin
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: Maheul
authors.initials: M
authors.lastname: Ploton
authors.affiliation: Cancer Research Institute BMC, Slovak Academy of Sciences , Dúbravská cesta 9, SK-845 05 Bratislava, Slovak Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Kretova
authors.affiliation: Université Rennes 1 , F-35042 Rennes, France.|UMR6290 CNRS, Team SP@RTE, Campus de Beaulieu, F-35042 Rennes, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Palierne
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
authors.affiliation: Cancer Research Institute BMC, Slovak Academy of Sciences , Dúbravská cesta 9, SK-845 05 Bratislava, Slovak Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Barath
authors.affiliation: B.S.R.C. "Alexander Fleming" , 34 Fleming Street, 16672 Vari, Greece.
authors.forename: Iannis
authors.initials: I
authors.lastname: Talianidis
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
authors.affiliation: European Genomic Institute for Diabetes (EGID), FR 3508, F-59000 Lille, France.|Inserm UMR U1011, F-59000 Lille, France.|Université Lille 2 , F-59000 Lille, France.|Institut Pasteur de Lille , F-59019 Lille, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Eeckhoute
authors.affiliation: Université Rennes 1 , F-35042 Rennes, France.|UMR6290 CNRS, Team SP@RTE, Campus de Beaulieu, F-35042 Rennes, France.
authors.forename: Gilles
authors.identifier: 0000-0001-6115-4140
authors.initials: G
authors.lastname: Salbert
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000818:Animals; D001665:Binding Sites; D051837:COUP Transcription Factor II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D054852:Small Molecule Libraries
chemical_list: D051837:COUP Transcription Factor II; D054852:Small Molecule Libraries