Functional interactions between Stat5 and the glucocorticoid receptor
Open accessAbstract
Signal transduction pathways enable extracellular signals to activate latent transcription factors in the cytoplasm of cells. Dimerization, nuclear localization and binding to specific DNA sequences result in the induction of gene transcription by these proteins. These events are necessary for the functioning of the JAK/STAT pathway and of the glucocorticoid-receptor pathway. In the former, the protein Stat5, which is a member of a family of signal transducers and activators of transcription, is activated by cytokines, hormones and growth factors. These polypeptide ligands bind at the outside of the cell to specific transmembrane receptors and activate intracellular Janus protein tyrosine kinases (JAKs) to tyrosine-phosphorylate STAT proteins; interaction with the SH2 domain of the dimerization partner then confers the ability to bind to DNA at the STAT-response element and induce transcription. In the glucocorticoid-receptor pathway, the receptor interacts with its steroid hormone ligand in the cytoplasm, undergoes an allosteric change that enables the hormone receptor complex to bind to specific DNA-response elements (glucocorticoid response elements, or GRE) and modulate transcription. Although these pathways appear to be unrelated, we show here that the glucocorticoid receptor can act as a transcriptional co-activator for Stat5 and enhance Stat5-dependent transcription. Stat5 forms a complex with the glucocorticoid receptor which binds to DNA independently of the GRE. This complex formation between Stat5 and the glucocorticoid receptor diminishes the glucocorticoid response of a GRE-containing promoter.
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Although STATs bind a similar DNA binding site, they may interact with co-activators or co-repressors to regulate different sets of their own downstream targets.
“Although they bind to a similar DNA binding site, STATs may interact with co-activator or co-repressor to regulate different sets of their own downstream targets (5”
From STAT3 Contributes to the Mitogenic Response of Hepatocytes during Liver Regeneration (2002) · cites this paper as [42]
The paper reports that the glucocorticoid receptor acts as a co-activator for Stat5 and proposes that different co-activators could contribute to signaling specificity. It does not establish that STAT family members bind similar DNA sites or interact with co-repressors to regulate distinct sets of downstream targets (section “Functional interactions between Stat5 and the glucocorticoid receptor”; page unavailable in our copy). (LLM, conf=0.85)
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- Authors
- Stöcklin, E., Wissler, M., Gouilleux, F., & Groner, B.
- Affiliations
- University of Freiburg (DE)
- ORCID
- Gouilleux, Fabrice
- Venue
- Nature
- Published
- 1996-10
- Volume
- 383
- Issue
- 6602
- Pages
- 726-728
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1977176665
- Cited by
- 675
- References
- 1
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 6 · 2023: 5 · 2022: 10 · 2021: 8 · 2020: 3 · 2019: 13 · 2018: 9 · 2017: 9 · 2016: 12 · 2015: 17 · 2014: 13 · 2013: 14 · 2012: 19
- FWCI
- 19.37
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- FreiDok plus (Universitätsbibliothek Freiburg) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- STAT5, glucocorticoid receptor, transcriptional coactivation, JAK/STAT signaling, glucocorticoid response element, transcriptional regulation, protein-protein interaction, steroid hormone receptors, gene transcription
- MeSH terms
- Animals, beta-Galactosidase, Caseins, DNA-Binding Proteins, Gene Expression Regulation, Luciferases, Milk Proteins, Receptors, Glucocorticoid, Repetitive Sequences, Nucleic Acid, Transfection, Signal Transduction, Trans-Activators, COS Cells, Tumor Suppressor Proteins, STAT5 Transcription Factor
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