Inactivation of the Nuclear Orphan Receptor COUP-TFII by Small Chemicals

被引：15

作者：

Le Guevel, Remy ^{[1
,2
,3
]}

Oger, Frederik ^{[4
,5
,6
,7
]}

Martinez-Jimenez, Celia P. ^{[8
]}

Bizot, Maud ^{[1
,2
]}

Gheeraert, Celine ^{[4
,5
,6
,7
]}

Firmin, Francois ^{[4
,5
,6
,7
]}

Ploton, Maheul ^{[4
,5
,6
,7
]}

Kretova, Miroslava ^{[9
]}

Palierne, Gaelle ^{[1
,2
]}

Staels, Bart ^{[4
,6
,7
]}

Barath, Peter ^{[5
,9
]}

Talianidis, Iannis ^{[8
]}

Lefebvre, Philippe ^{[4
,5
,6
,7
]}

Eeckhoute, Jerome ^{[4
,5
,6
,7
]}

Salbert, Gilles ^{[1
,2
]}

机构：

[1] Univ Rennes 1, F-35042 Rennes, France

[2] CNRS, Team SP RTE, UMR6290, Campus Beaulieu, F-35042 Rennes, France

[3] INSERM, CNRS, UMS 3480, SFR Biosit,US 018, Campus Villejean, F-35043 Rennes, France

[4] EGID, FR 3508, F-59000 Lille, France

[5] INSERM, UMR U1011, F-59000 Lille, France

[6] Univ Lille 2, F-59000 Lille, France

[7] Inst Pasteur, F-59019 Lille, France

[8] BSRC Alexander Fleming, 34 Fleming St, Vari 16672, Greece

[9] Slovak Acad Sci, Canc Res Inst BMC, Dubravska Cesta 9, SK-84505 Bratislava, Slovakia

来源：

ACS CHEMICAL BIOLOGY | 2017年 / 12卷 / 03期

关键词：

GENE-EXPRESSION; TRANSCRIPTIONAL ACTIVATION; STRUCTURAL BASIS; BINDING-SITES; NURR1; PROTEIN; IDENTIFICATION; PREDICTION; LIGANDS; MEMBERS;

D O I：

10.1021/acschembio.6b00593

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：654 / 663

页数：10

共 36 条

[1] COUP-TFI (Chicken ovalbumin upstream promoter-transcription factor I) regulates cell migration and axogenesis in differentiating P19 embryonal carcinoma cells [J].