Differences in nuclear retention characteristics of agonist-activated glucocorticoid receptor may determine specific responses
We studied the glucocorticoid response to the synthetic steroid pregna-1,4-diene-11β-ol-3,20-dione (ΔHOP) in several cell types and correlated its biological effect with the ability of the glucocorticoid receptor (GR) to be retained in the nuclear compartment. We observed that the ΔHOP-transformed G...
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Elsevier
2002
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| 040 | |a Scopus |b spa |c AR-BaUEN |d AR-BaUEN | ||
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| 100 | 1 | |a Vicent, G.P. | |
| 245 | 1 | 0 | |a Differences in nuclear retention characteristics of agonist-activated glucocorticoid receptor may determine specific responses |
| 260 | |b Elsevier |c 2002 | ||
| 270 | 1 | 0 | |m Galigniana, M.D.; 1301 Med. Sci. Research Building III, Department of Pharmacology, Univ. of Michigan Medical School, Ann Arbor, MI 48109, United States; email: mgali@umich.edu |
| 506 | |2 openaire |e Política editorial | ||
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| 520 | 3 | |a We studied the glucocorticoid response to the synthetic steroid pregna-1,4-diene-11β-ol-3,20-dione (ΔHOP) in several cell types and correlated its biological effect with the ability of the glucocorticoid receptor (GR) to be retained in the nuclear compartment. We observed that the ΔHOP-transformed GR was diffusely distributed in the nucleus compared to the discrete structures observed for the dexamethasone (DEX)-transformed GR. Despite the fact that the receptor was entirely nuclear upon binding of each steroid and exhibited identical nuclear export rates, a greater amount of ΔHOP-transformed GR was recovered in the cytoplasmic fraction after hypotonic cell lysis. Furthermore, accelerated nuclear export of GR was evidenced in digitonin-permeabilized cells treated with ATP and molybdate. Inasmuch as limited trypsinization of DEX-GR and ΔHOP-GR complexes yielded different proteolytic products, we conclude that GR undergoes a differential conformational change upon binding of each ligand. We propose that these conformational differences may consequently lead to changes of stability in the interaction of the GR with chromatin. Therefore, the dynamic exchange of liganded GR with chromatin is likely to have significant consequences for the observed pleiotropic physiological responses triggered by glucocorticoid ligands, not only in different tissues but also in the same cell type. © 2002 Elsevier Science (USA). |l eng | |
| 536 | |a Detalles de la financiación: We thank Dr. M. Beato (Philipps Universität, Marburg, Germany) for providing the Rentro-1 cell line, Dr. H. Green (Harvard University) for providing the 3T3-F442A cell line (courtesy of Dr. J. Schwartz, University of Michigan), and Dr. W. B. Pratt (University of Michigan) for the kind gift of UP30 antibody. We are also indebted to Dr. G. Burton and Dr. C. P. Lantos (Universidad de Buenos Aires) for their critical and constructive comments. Part of this work was supported by grants from Fundación Antorchas and Ministerio de Salud Pública de la República Argentina to A.P. | ||
| 593 | |a Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina | ||
| 593 | |a Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina | ||
| 593 | |a Department of Physiology, University of Michigan Medical School, Ann Arbor, Mi 48109, United States | ||
| 593 | |a Department of Pharmacology, University of Michigan, Medical School, Ann Arbor, Mi 48109, United States | ||
| 690 | 1 | 0 | |a ADENOSINE TRIPHOSPHATE |
| 690 | 1 | 0 | |a DEXAMETHASONE |
| 690 | 1 | 0 | |a DIGITONIN |
| 690 | 1 | 0 | |a GLUCOCORTICOID RECEPTOR |
| 690 | 1 | 0 | |a MIFEPRISTONE |
| 690 | 1 | 0 | |a MOLYBDIC ACID |
| 690 | 1 | 0 | |a PREGNA 1,4 11BETA OL 3,20 DIONE |
| 690 | 1 | 0 | |a STEROID |
| 690 | 1 | 0 | |a UNCLASSIFIED DRUG |
| 690 | 1 | 0 | |a ANIMAL CELL |
| 690 | 1 | 0 | |a ANIMAL TISSUE |
| 690 | 1 | 0 | |a APOPTOSIS |
| 690 | 1 | 0 | |a ARTICLE |
| 690 | 1 | 0 | |a CELL MEMBRANE PERMEABILITY |
| 690 | 1 | 0 | |a CELL PERMEABILIZATION |
| 690 | 1 | 0 | |a CHROMATIN |
| 690 | 1 | 0 | |a CONFORMATION |
| 690 | 1 | 0 | |a CONTROLLED STUDY |
| 690 | 1 | 0 | |a CYTOLYSIS |
| 690 | 1 | 0 | |a DOSE RESPONSE |
| 690 | 1 | 0 | |a DRUG EFFECT |
| 690 | 1 | 0 | |a LIGAND BINDING |
| 690 | 1 | 0 | |a MALE |
| 690 | 1 | 0 | |a MOUSE |
| 690 | 1 | 0 | |a NONHUMAN |
| 690 | 1 | 0 | |a PLEIOTROPY |
| 690 | 1 | 0 | |a PRIORITY JOURNAL |
| 690 | 1 | 0 | |a PROTEIN DEGRADATION |
| 690 | 1 | 0 | |a RAT |
| 653 | 0 | 0 | |a ru 486, Amersham, United States |
| 700 | 1 | |a Pecci, A. | |
| 700 | 1 | |a Ghini, A. | |
| 700 | 1 | |a Piwien-Pilipuk, G. | |
| 700 | 1 | |a Galigniana, M.D. | |
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