Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
Copyright policy )Glucocorticoid Receptor-mediated transactivation is hampered by Striatin-3, a novel interaction partner of the receptor
AbstractThe 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.
- Ghent University Belgium
- VIB Belgium
- Cancer Research Institute Ghent Belgium
Transcriptional Activation, GENES, Science, Down-Regulation, KINASE STRIPAK, Autoantigens, Article, MECHANISMS, Receptors, Glucocorticoid, INFLAMMATION, Medicine and Health Sciences, Humans, TRANSCRIPTION, Protein Interaction Maps, Protein Phosphatase 2, Phosphorylation, PHOSPHORYLATION, Cell Nucleus, Binding Sites, IDENTIFICATION, Q, TRANSREPRESSION, R, Biology and Life Sciences, PROTEIN PHOSPHATASE 2A, HEK293 Cells, FACTORS, A549 Cells, Medicine, Calmodulin-Binding Proteins, MINERALOCORTICOID RECEPTOR, Protein Multimerization, HeLa Cells
Transcriptional Activation, GENES, Science, Down-Regulation, KINASE STRIPAK, Autoantigens, Article, MECHANISMS, Receptors, Glucocorticoid, INFLAMMATION, Medicine and Health Sciences, Humans, TRANSCRIPTION, Protein Interaction Maps, Protein Phosphatase 2, Phosphorylation, PHOSPHORYLATION, Cell Nucleus, Binding Sites, IDENTIFICATION, Q, TRANSREPRESSION, R, Biology and Life Sciences, PROTEIN PHOSPHATASE 2A, HEK293 Cells, FACTORS, A549 Cells, Medicine, Calmodulin-Binding Proteins, MINERALOCORTICOID RECEPTOR, Protein Multimerization, HeLa Cells
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