Cited by 1,068Estrogen and related hormone effectsGenomics and Chromatin DynamicsAdrenal Hormones and Disorders

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DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival

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Reichardt, Holger M, Kaestner, Klaus H, Tuckermann, Jan, Kretz, Oliver, Wessely, Oliver, Bock, Rudolf, Gass, Peter, Schmid, Wolfgang, Herrlich, Peter, Angel, Peter, Schütz, Günther·1998·Cell

DOI 10.1016/s0092-8674(00)81183-6

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Abstract

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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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
ORCID: Reichardt, Holger M
Kaestner, Klaus H
Tuckermann, Jan
Kretz, Oliver
Wessely, Oliver
Angel, Peter
Venue: Cell
Publisher: Elsevier BV
Published: 1998-05
Volume: 93
Issue: 4
Pages: 531-541
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/s0092-8674(00)81183-6
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: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor, 1076 d)
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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DNA Binding of the Glucocorticoid Receptor Is Not Essential for Survival

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