Nuclear export of glucocorticoid receptor is enhanced by c-Jun N-terminal kinase-mediated phosphorylation
Open accessAbstract
The c-Jun N-terminal kinase (JNK) phosphorylates the glucocorticoid receptor (GR) and inhibits GR-mediated transcription. However, the biological effect of the GR phosphorylation remains unknown. Here we demonstrate that activated JNK phosphorylates human GR at Ser226 and enhances its nuclear export after withdrawal of a ligand for GR, dexamethasone. At 1 h after dexamethasone withdrawal, green fluorescent protein-GR molecules were mostly retained at the nucleus, whereas UV exposure enhanced its nuclear export, and approximately 30–40% of cells revealed distinct nuclear export. JNK overexpression alone mimics UV exposure and enhanced GR export accompanied by inhibition of GR-mediated transcription. However, mutation of the Ser226 JNK phosphorylation site in GR abrogated UV-mediated enhancement of GR nuclear export. Furthermore, overexpression of a dominant negative SEK1 mutant also abrogated the effects of UV exposure on GR export. Taken together, these findings suggest that JNK-mediated phosphorylation of the GR-Ser226 enhances GR nuclear export and may contribute to termination of GR-mediated transcription.
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Activation of JNK results in increased nuclear export of GR.
“activation of JNK has also been shown to result in increased nuclear export of GR.63”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [63]
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- Authors
- Itoh, M., Adachi, M., Yasui, H., Takekawa, M., Tanaka, H., & Imai, K.
- Affiliations
- Sapporo Medical University (JP)
- Division of Molecular Cell Signaling (M.T.), Tokyo 108-8639, Japan
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Adachi, M.
- Venue
- Molecular Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2002-10-01
- Volume
- 16
- Issue
- 10
- Pages
- 2382-2392
- ISSN
- 0888-8809 (ISSN-L)
- 1944-9917
- OpenAlex
- W2162451875
- Cited by
- 238
- References
- 3
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 2 · 2023: 11 · 2022: 9 · 2021: 8 · 2020: 8 · 2019: 11 · 2018: 8 · 2017: 12 · 2016: 9 · 2015: 8 · 2014: 4 · 2013: 18 · 2012: 14
- FWCI
- 5.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- glucocorticoid receptor, c-Jun N-terminal kinase, JNK phosphorylation, nuclear export, UV exposure, SEK1, transcription termination, ligand-independent receptor activity
- MeSH terms
- Alanine, Amino Acid Sequence, Animals, Dexamethasone, Enzyme Activation, Fatty Acids, Unsaturated, HeLa Cells, Humans, Luminescent Proteins, Molecular Sequence Data, Mutation, Phosphorylation, Receptors, Glucocorticoid, Recombinant Proteins, Serine, Transcription, Genetic, Ultraviolet Rays, COS Cells, Mitogen-Activated Protein Kinases, Active Transport, Cell Nucleus, JNK Mitogen-Activated Protein Kinases, Green Fluorescent Proteins
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