Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor

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. R...

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Autores principales:	Ioanna Petta, Nadia Bougarne, Jolien Vandewalle, Lien Dejager, Sofie Vandevyver, Marlies Ballegeer, Sofie Desmet, Jonathan Thommis, Lode De Cauwer, Sam Lievens, Claude Libert, Jan Tavernier, Karolien De Bosscher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/77db01aba2e84ce3beeed9e7bccc5c85
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spelling	oai:doaj.org-article:77db01aba2e84ce3beeed9e7bccc5c852021-12-02T11:52:17ZGlucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor10.1038/s41598-017-09246-62045-2322https://doaj.org/article/77db01aba2e84ce3beeed9e7bccc5c852017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09246-6https://doaj.org/toc/2045-2322Abstract 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.Ioanna PettaNadia BougarneJolien VandewalleLien DejagerSofie VandevyverMarlies BallegeerSofie DesmetJonathan ThommisLode De CauwerSam LievensClaude LibertJan TavernierKarolien De BosscherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ioanna Petta Nadia Bougarne Jolien Vandewalle Lien Dejager Sofie Vandevyver Marlies Ballegeer Sofie Desmet Jonathan Thommis Lode De Cauwer Sam Lievens Claude Libert Jan Tavernier Karolien De Bosscher Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
description	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.
format	article
author	Ioanna Petta Nadia Bougarne Jolien Vandewalle Lien Dejager Sofie Vandevyver Marlies Ballegeer Sofie Desmet Jonathan Thommis Lode De Cauwer Sam Lievens Claude Libert Jan Tavernier Karolien De Bosscher
author_facet	Ioanna Petta Nadia Bougarne Jolien Vandewalle Lien Dejager Sofie Vandevyver Marlies Ballegeer Sofie Desmet Jonathan Thommis Lode De Cauwer Sam Lievens Claude Libert Jan Tavernier Karolien De Bosscher
author_sort	Ioanna Petta
title	Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
title_short	Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
title_full	Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
title_fullStr	Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
title_full_unstemmed	Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
title_sort	glucocorticoid receptor-mediated transactivation is hampered by striatin-3, a novel interaction partner of the receptor
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/77db01aba2e84ce3beeed9e7bccc5c85
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Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor

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