ArticleMolecular and cellular biology1999
Discrimination between NL1- and NL2-mediated nuclear localization of the glucocorticoid receptor.
Article in Molecular and cellular biology, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Generalized glucocorticoid resistance: clinical aspects, molecular mechanisms, and implications of a rare genetic disorder.The Journal of clinical endocrinology and metabolism · 2008Pooled it
- Cervical sympathetic block regulates early systemic inflammatory response in severe trauma patients.Medical science monitor : international medical journal of experimental and clinical research · 2013Trial
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- Novel Perspectives of TSLP and RXR Signaling in Corticosteroid-Resistant Asthma: Updates on TSLP Blockers.Current medicinal chemistry · 2025Review
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- Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor.Nature structural & molecular biology · 2023Article
- Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?Endocrine reviews · 2023Review
- Androgen receptor nucleocytoplasmic trafficking - A one-way journey.Molecular and cellular endocrinology · 2023Review
- Quantification of transcriptome changes to investigate the role of glucocorticoid receptor-RNA binding during dexamethasone treatment.BMC research notes · 2023Article
- UBR5 forms ligand-dependent complexes on chromatin to regulate nuclear hormone receptor stability.Molecular cell · 2023Article
- RNA binding by the glucocorticoid receptor attenuates dexamethasone-induced gene activation.Scientific reports · 2023Article
- Context-Dependent Role of Glucocorticoid Receptor Alpha and Beta in Breast Cancer Cell Behaviour.Cells · 2023Article
- Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the Glucocorticoid Receptor.bioRxiv : the preprint server for biology · 2023Article
- Mechanisms behind context-dependent role of glucocorticoids in breast cancer progression.Cancer metastasis reviews · 2022Review
- Importins involved in the nuclear transportation of steroid hormone receptors:Frontiers in endocrinology · 2022Article
- Transportin-2 plays a critical role in nucleocytoplasmic shuttling of oestrogen receptor-α.Scientific reports · 2020Article
- Article
- NL1 expression level in Nrx1β and the excitability of PV interneurons in mice with POCD.Experimental and therapeutic medicine · 2019Article
- Membrane-initiated nuclear trafficking of the glucocorticoid receptor in hypothalamic neurons.Steroids · 2019Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glucocorticoid receptor (GR) cycles between a free liganded form that is localized to the nucleus and a heat shock protein (hsp)-immunophilin-complexed, unliganded form that is usually localized to the cytoplasm but that can also be nuclear. In addition, rapid nucleocytoplasmic exchange or shuttling of the receptor underlies its localization. Nuclear import of liganded GR is mediated through a well-characterized sequence, NL1, adjacent to the receptor DNA binding domain and a second, uncharacterized motif, NL2, that overlaps with the ligand binding domain. In this study we report that rapid nuclear import (half-life [t1/2] of 4 to 6 min) of agonist- and antagonist-treated GR and the localization of unliganded, hsp-associated GRs to the nucleus in G0 are mediated through NL1 and correlate with the binding of GR to pendulin/importin alpha. By contrast, NL2-mediated nuclear transfer of GR occurred more slowly (t1/2 = 45 min to 1 h), was agonist specific, and appeared to be independent of binding to importin alpha. Together, these results suggest that NL2 mediates the nuclear import of GR through an alternative nuclear import pathway. Nuclear export of GR was inhibited by leptomycin B, suggesting that the transfer of GR to the cytoplasm is mediated through the CRM1-dependent pathway. Inhibition of GR nuclear export by leptomycin B enhanced the nuclear localization of both unliganded, wild-type GR and hormone-treated NL1(-) GR. These results highlight that the subcellular localization of both liganded and unliganded GRs is determined, at least in part, by a flexible equilibrium between the rates of nuclear import and export.
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