Abstract

The transcriptional activity of the glucocorticoid receptor (GR) is co-determined by its ability to recruit a vast and varying number of cofactors. We here identify Striatin-3 (STRN3) as a novel interaction partner of GR that interferes with GR’s ligand-dependent transactivation capacity. Remarkably, STRN3 selectively affects only GR-dependent transactivation and leaves GR-dependent transrepression mechanisms unhampered. We found that STRN3 down-regulates GR transactivation by an additional recruitment of the catalytic subunit of protein phosphatase 2A (PPP2CA) to GR. We hypothesize the existence of a functional trimeric complex in the nucleus, able to dephosphorylate GR at serine 211, a known marker for GR transactivation in a target gene-dependent manner. The presence of STRN3 appears an absolute prerequisite for PPP2CA to engage in a complex with GR. Herein, the C-terminal domain of GR is essential, reflecting ligand-dependency, yet other receptor parts are also needed to create additional contacts with STRN3.

Details

Title
Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
Author
Petta, Ioanna 1 ; Bougarne, Nadia 2 ; Vandewalle, Jolien 3 ; Dejager, Lien 3 ; Vandevyver, Sofie 3 ; Ballegeer, Marlies 3 ; Desmet, Sofie 2 ; Thommis, Jonathan 2 ; De Cauwer, Lode 2 ; Lievens, Sam 4 ; Libert, Claude 3 ; Tavernier, Jan 5 ; De Bosscher, Karolien 6 

 Receptor Research Laboratories, Cytokine Receptor Lab, VIB, Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium; Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium 
 Receptor Research Laboratories, Cytokine Receptor Lab, VIB, Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium; Receptor Research Laboratories, Nuclear Receptor Lab, VIB, Medical Biotechnology Center, Ghent, Belgium 
 Center for Inflammation Research, VIB, Ghent, Belgium; Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium 
 Receptor Research Laboratories, Cytokine Receptor Lab, VIB, Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium 
 Receptor Research Laboratories, Cytokine Receptor Lab, VIB, Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium 
 Receptor Research Laboratories, Cytokine Receptor Lab, VIB, Center for Medical Biotechnology, Ghent, Belgium; Department of Biochemistry, Ghent University, Ghent, Belgium; Receptor Research Laboratories, Nuclear Receptor Lab, VIB, Medical Biotechnology Center, Ghent, Belgium; Cancer Research Institute Ghent (CRIG), Ghent, Belgium 
Pages
1-15
Publication year
2017
Publication date
Aug 2017
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
1957279511
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.