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

Ioanna Petta (UGent) , Nadia Bougarne (UGent) , Jolien Vandewalle (UGent) , Lien Dejager (UGent) , Sofie Vandevyver (UGent) , Marlies Ballegeer (UGent) , Sofie Desmet (UGent) , Jonathan Thommis (UGent) , Lode De Cauwer (UGent) , Sam Lievens (UGent) , et al.
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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.
Keywords
PROTEIN PHOSPHATASE 2A, MINERALOCORTICOID RECEPTOR, TRANSCRIPTION, FACTORS, KINASE STRIPAK, INFLAMMATION, PHOSPHORYLATION, MECHANISMS, GENES, TRANSREPRESSION, IDENTIFICATION

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Chicago
Petta, Ioanna, Nadia Bougarne, Jolien Vandewalle, Lien Dejager, Sofie Vandevyver, Marlies Ballegeer, Sofie Desmet, et al. 2017. “Glucocorticoid Receptor-mediated Transactivation Is Hampered by Striatin-3, a Novel Interaction Partner of the Receptor.” Scientific Reports 7.
APA
Petta, I., Bougarne, N., Vandewalle, J., Dejager, L., Vandevyver, S., Ballegeer, M., Desmet, S., et al. (2017). Glucocorticoid receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor. SCIENTIFIC REPORTS, 7.
Vancouver
1.
Petta I, Bougarne N, Vandewalle J, Dejager L, Vandevyver S, Ballegeer M, et al. Glucocorticoid receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor. SCIENTIFIC REPORTS. 2017;7.
MLA
Petta, Ioanna, Nadia Bougarne, Jolien Vandewalle, et al. “Glucocorticoid Receptor-mediated Transactivation Is Hampered by Striatin-3, a Novel Interaction Partner of the Receptor.” SCIENTIFIC REPORTS 7 (2017): n. pag. Print.
@article{8533752,
  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.},
  articleno    = {8941},
  author       = {Petta, Ioanna and Bougarne, Nadia and Vandewalle, Jolien and Dejager, Lien and Vandevyver, Sofie and Ballegeer, Marlies and Desmet, Sofie and Thommis, Jonathan and De Cauwer, Lode and Lievens, Sam and Libert, Claude and Tavernier, Jan and De Bosscher, Karolien},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  keyword      = {PROTEIN PHOSPHATASE 2A,MINERALOCORTICOID RECEPTOR,TRANSCRIPTION,FACTORS,KINASE STRIPAK,INFLAMMATION,PHOSPHORYLATION,MECHANISMS,GENES,TRANSREPRESSION,IDENTIFICATION},
  language     = {eng},
  pages        = {15},
  title        = {Glucocorticoid receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor},
  url          = {http://dx.doi.org/10.1038/s41598-017-09246-6},
  volume       = {7},
  year         = {2017},
}

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