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DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival
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Transcriptional regulation by the glucocorticoid receptor (GR) is essential for survival. Since the GR can influence transcription both through DNA-binding-dependent and -independent mechanisms, we attempted to assess their relative importance in vivo. In order to separate these modes of action, we introduced the point mutation A458T into the GR by gene targeting using the Cre/loxP system. This mutation impairs dimerization and therefore GRE-dependent transactivation while functions that require cross-talk with other transcription factors, such as transrepression of AP-1-driven genes, remain intact. In contrast to GR-/- mice, these mutants termed GRdim are viable, revealing the in vivo relevance of DNA-binding-independent activities of the GR.
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“Contrastingly, other findings indicate that in GRdim mice NF-κB and AP-1 target genes can still be silenced by GCs (107, 108), that the GC-inducible gene MKP-1 is normally expressed in macrophages (82) and that irritant dermatitis can successfully be treated with GCs (22).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [107]
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“Initial evidence suggested that classic transactivation by GRs was defective in these mice and that this mechanism was required for the full range of GC immunosuppressive actions (107, 108).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [107]
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Metadata
- Authors
- Reichardt, H. M., Kaestner, K. H., Tuckermann, J., Kretz, O., Wessely, O., Bock, R., Gass, P., Schmid, W., Herrlich, P., Angel, P., & Schütz, G.
- Affiliations
- German Cancer Research Center (DE)
- Saarland University (DE)
- Corresponding author
- Schütz, Günther
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1998-05
- Volume
- 93
- Issue
- 4
- Pages
- 531-541
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1997510672
- Cited by
- 1,068
- References
- 54
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 7 · 2023: 16 · 2022: 21 · 2021: 22 · 2020: 21 · 2019: 28 · 2018: 24 · 2017: 26 · 2016: 18 · 2015: 24 · 2014: 40 · 2013: 36 · 2012: 34
- FWCI
- 38.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoid receptor, DNA binding, receptor dimerization, gene targeting, Cre-loxP system, transcriptional regulation, survival
- MeSH terms
- Amino Acid Sequence, Animals, Cells, Cultured, Dexamethasone, DNA, Feedback, Gene Expression Regulation, Glucocorticoids, Hypothalamo-Hypophyseal System, Molecular Sequence Data, Pituitary-Adrenal System, Protein Binding, Receptors, Glucocorticoid, T-Lymphocytes, Transcription, Genetic, Erythroid Precursor Cells, Apoptosis, Point Mutation, Mice, Knockout, Mice
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