Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor
- Autores
- Piwien Pilipuk, Graciela; Vinson, Gavin P.; Gomez Sanchez, Celso; Galigniana, Mario Daniel
- Año de publicación
- 2007
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- 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 (t0.5 = 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.
Fil: Piwien Pilipuk, Graciela. Fundación Instituto Leloir; Argentina
Fil: Vinson, Gavin P.. University Of London; Reino Unido
Fil: Gomez Sanchez, Celso. University Of Mississippi; Estados Unidos
Fil: Galigniana, Mario Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Fundación Instituto Leloir; Argentina - Materia
-
Aldosterone
Cell Nucleus
Nuclear Localization Signals
Mineralocorticoid Receptors - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/27824
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Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptorPiwien Pilipuk, GracielaVinson, Gavin P.Gomez Sanchez, CelsoGaligniana, Mario DanielAldosteroneCell NucleusNuclear Localization SignalsMineralocorticoid Receptorshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In 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 (t0.5 = 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.Fil: Piwien Pilipuk, Graciela. Fundación Instituto Leloir; ArgentinaFil: Vinson, Gavin P.. University Of London; Reino UnidoFil: Gomez Sanchez, Celso. University Of Mississippi; Estados UnidosFil: Galigniana, Mario Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Fundación Instituto Leloir; ArgentinaAmerican Chemical Society2007info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/27824Piwien Pilipuk, Graciela; Vinson, Gavin P.; Gomez Sanchez, Celso; Galigniana, Mario Daniel; Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor; American Chemical Society; Biochemistry; 46; 5; -1-2007; 1389-13970006-29601520-4995CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/bi0621819info:eu-repo/semantics/altIdentifier/doi/10.1021/bi0621819info:eu-repo/semantics/altIdentifier/pmid/17260968info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:46:02Zoai:ri.conicet.gov.ar:11336/27824instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:46:03.141CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
title |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
spellingShingle |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor Piwien Pilipuk, Graciela Aldosterone Cell Nucleus Nuclear Localization Signals Mineralocorticoid Receptors |
title_short |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
title_full |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
title_fullStr |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
title_full_unstemmed |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
title_sort |
Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor |
dc.creator.none.fl_str_mv |
Piwien Pilipuk, Graciela Vinson, Gavin P. Gomez Sanchez, Celso Galigniana, Mario Daniel |
author |
Piwien Pilipuk, Graciela |
author_facet |
Piwien Pilipuk, Graciela Vinson, Gavin P. Gomez Sanchez, Celso Galigniana, Mario Daniel |
author_role |
author |
author2 |
Vinson, Gavin P. Gomez Sanchez, Celso Galigniana, Mario Daniel |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Aldosterone Cell Nucleus Nuclear Localization Signals Mineralocorticoid Receptors |
topic |
Aldosterone Cell Nucleus Nuclear Localization Signals Mineralocorticoid Receptors |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/3.1 https://purl.org/becyt/ford/3 |
dc.description.none.fl_txt_mv |
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 (t0.5 = 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. Fil: Piwien Pilipuk, Graciela. Fundación Instituto Leloir; Argentina Fil: Vinson, Gavin P.. University Of London; Reino Unido Fil: Gomez Sanchez, Celso. University Of Mississippi; Estados Unidos Fil: Galigniana, Mario Daniel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Fundación Instituto Leloir; Argentina |
description |
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 (t0.5 = 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. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/27824 Piwien Pilipuk, Graciela; Vinson, Gavin P.; Gomez Sanchez, Celso; Galigniana, Mario Daniel; Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor; American Chemical Society; Biochemistry; 46; 5; -1-2007; 1389-1397 0006-2960 1520-4995 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/27824 |
identifier_str_mv |
Piwien Pilipuk, Graciela; Vinson, Gavin P.; Gomez Sanchez, Celso; Galigniana, Mario Daniel; Evidence for NL1-independent nuclear translocation of the mineralocorticoid receptor; American Chemical Society; Biochemistry; 46; 5; -1-2007; 1389-1397 0006-2960 1520-4995 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/bi0621819 info:eu-repo/semantics/altIdentifier/doi/10.1021/bi0621819 info:eu-repo/semantics/altIdentifier/pmid/17260968 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
American Chemical Society |
publisher.none.fl_str_mv |
American Chemical Society |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
collection |
CONICET Digital (CONICET) |
instname_str |
Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.name.fl_str_mv |
CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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1844613438539563008 |
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13.070432 |