Nucleocytoplasmic Trafficking of Steroid-free Glucocorticoid Receptor
| Autor: | Yvonne A. Lefebvre, Raymond Tse, Robert J. G. Haché, Joanne G.A. Savory, Terry Reich |
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| Rok vydání: | 1999 |
| Předmět: |
Cytoplasm
Hydrocortisone Transcription Genetic Protein Conformation Biology Ligands Biochemistry Mice Structure-Activity Relationship Hormone Antagonists Receptors Glucocorticoid Glucocorticoid receptor Transcription (biology) Heat shock protein Tumor Cells Cultured medicine Animals Nuclear membrane Receptor Molecular Biology Heat-Shock Proteins Fluorescent Dyes Cell Nucleus COS cells Biological Transport 3T3 Cells Cell Biology Rats Cell biology Mifepristone medicine.anatomical_structure COS Cells Bisbenzimidazole Nucleus |
| Zdroj: | Journal of Biological Chemistry. 274:1432-1439 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.274.3.1432 |
| Popis: | Glucocorticoid receptor (GR) recycles between an inactive form complexed with heat shock proteins (hsps) and localized to the cytoplasm and a free liganded form that regulates specific gene transcription in the nucleus. We report here that, contrary to previous assumptions, association of GR into hsp-containing complexes is not sufficient to prevent the shuttling or trafficking of the GR across the nuclear membrane. Following the withdrawal of treatment with cortisol or the hormone antagonist RU486, GRs recycled rapidly into hsp-associated, hormone-responsive complexes. However, cortisol-withdrawn receptors redistributed to the cytoplasm very slowly (t(1)/(2) = 8-9 h) and RU486-withdrawn receptors not at all. Persistent localization of these GRs to the nucleus was not due to a gross defect in export, since in both instances the complexed nuclear GRs transferred efficiently between heterokaryon nuclei. Moreover, the addition of a nuclear retention signal to the N terminus of GR induced the transfer of naive receptor to the nucleus in the absence of steroid. These results suggest that the localization of GR to the cytoplasm is determined by fine control of the rates of transfer of GR across the nuclear membrane and/or by active retention that occurs independently from the association of GR with hsps. |
| Databáze: | OpenAIRE |
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