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Abstract:

In the absence of hormone, corticosteroid receptors are primarily located in the cytoplasm, and they rapidly accumulate in the nucleus (t0.5 = 5 min) upon ligand binding. It is generally believed that the dissociation of hsp90 from the receptor is an absolute requirement for allowing its nuclear translocation. However, recent evidence suggests that hsp90 may remain associated with the glucocorticoid receptor during this process, and thus, the receptor nuclear localization signal (NLS) is not obscured by its presence. To determine the requirements for mineralocorticoid receptor (MR) nuclear transport, it was first shown that in rat kidney collecting duct cells, nuclear localization of MR in the presence of aldosterone was complete in 10 min. Although the hsp90 inhibitor radicicol delayed nuclear translocation, it did not prevent complete nuclear accumulation of MR at longer incubation times (t 0.5 = 30-40 min). MR carbamylation generates a non-steroid- transformed receptor that, in contrast to native MR, is very stable in cell-free systems. In contrast to the full nuclear translocation of aldosterone- transformed MR, only a fraction of the carbamylated MR became nuclear in digitonin-permeabilized cells even though its NLS is exposed. Furthermore, while preincubation of permeabilized cells with NL1 peptide or anti-NL1 antibody fully inhibited the nuclear translocation of NL1-tagged albumin, neither treatment fully inhibited MR nuclear translocation. We postulate that there are at least two possible mechanisms for MR nuclear translocation. One of them is hsp90- and NL1-dependent, and the other functions in a manner that is independent of the classical pathway. © 2007 American Chemical Society.

Registro:

Documento: Artículo
Título:Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor
Autor:Pilipuk, G.P.; Vinson, G.P.; Sanchez, C.G.; Galigniana, M.D.
Filiación:Fundación Instituto Leloir, Av. Patricias Argentinas 435, Buenos Aires C1405BWE, Argentina
Fundación Instituto Leloir, CONICET, Buenos Aires, Argentina
School of Biological Sciences, Queen Mary, University of London, London, United Kingdom
Division of Endocrinology, University of Mississippi Medical Center, Jackson, MS 39216, United States
Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Antibodies; Biological organs; Cells; Chemical bonds; Dissociation; Hormones; Proteins; Glucocorticoid receptors; Mineralocorticoid receptor (MR); Nuclear accumulation; Nuclear localization signals (NLS); Neurology; aldosterone; corticosteroid receptor; digitonin; heat shock protein 90; mineralocorticoid receptor; animal cell; article; carbamoylation; cell membrane permeability; cell nucleus; controlled study; cytoplasm; dissociation; kidney collecting tubule; ligand binding; mouse; nonhuman; nuclear localization signal; priority journal; protein localization; rat; Active Transport, Cell Nucleus; Aldosterone; Animals; HSP90 Heat-Shock Proteins; Kidney; Kinetics; Nuclear Localization Signals; Rats; Receptors, Mineralocorticoid; Rattus
Año:2007
Volumen:46
Número:5
Página de inicio:1389
Página de fin:1397
DOI: http://dx.doi.org/10.1021/bi0621819
Título revista:Biochemistry
Título revista abreviado:Biochemistry
ISSN:00062960
CODEN:BICHA
CAS:aldosterone, 52-39-1, 6251-69-0; digitonin, 11024-24-1; Aldosterone, 52-39-1; HSP90 Heat-Shock Proteins; Nuclear Localization Signals; Receptors, Mineralocorticoid
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00062960_v46_n5_p1389_Pilipuk

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Citas:

---------- APA ----------
Pilipuk, G.P., Vinson, G.P., Sanchez, C.G. & Galigniana, M.D. (2007) . Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor. Biochemistry, 46(5), 1389-1397.
http://dx.doi.org/10.1021/bi0621819
---------- CHICAGO ----------
Pilipuk, G.P., Vinson, G.P., Sanchez, C.G., Galigniana, M.D. "Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor" . Biochemistry 46, no. 5 (2007) : 1389-1397.
http://dx.doi.org/10.1021/bi0621819
---------- MLA ----------
Pilipuk, G.P., Vinson, G.P., Sanchez, C.G., Galigniana, M.D. "Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor" . Biochemistry, vol. 46, no. 5, 2007, pp. 1389-1397.
http://dx.doi.org/10.1021/bi0621819
---------- VANCOUVER ----------
Pilipuk, G.P., Vinson, G.P., Sanchez, C.G., Galigniana, M.D. Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor. Biochemistry. 2007;46(5):1389-1397.
http://dx.doi.org/10.1021/bi0621819