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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/27824

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network_name_str CONICET Digital (CONICET)
spelling 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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