Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Horm...
- Autores
- Gallo, Luciana Ines; Ghini, Alberto Antonio; Piwien Pilipuk, Graciela; Galigniana, Mario Daniel
- Año de publicación
- 2007
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The mineralocorticoid receptor (MR) forms oligomers with the heat-shock protein 90 (Hsp90) -based heterocomplex, which contains tetratricopeptide repeat (TPR) domain immunophilins (IMMs). Here we investigated the unknown biological role of IMMs in the MR·Hsp90 complex. Upon hormone binding, FKBP52 was greatly recruited to MR·Hsp90 complexes along with dynein motors, whereas FKBP51 was dissociated. Importantly, the Hsp90 inhibitor geldanamycin impaired the retrograde transport of MR, suggesting that the Hsp90·IMM·dynein molecular machinery is required for MR movement. To elucidate the mechanism of action of MR, the synthetic ligand 11,19-oxidoprogesterone was used as a tool. This steroid showed equivalent agonistic potency to natural agonists and was able to potentiate their mineralocorticoid action. Importantly, aldosterone binding recruited greater amounts of FKBP52 and dynein than 11,19-oxidoprogesterone binding to MR. Interestingly, 11,19-oxidoprogesterone binding also favored the selective recruitment of the IMM-like Ser/Thr phosphatase PP5. Each hormone/MR complex yielded different proteolytic peptide patterns, suggesting that MR acquires different conformations upon steroid binding. Also, hormone/MR complexes showed different nuclear translocation rates and subnuclear redistribution. All these observations may be related to the selective swapping of associated factors. We conclude that (a) the Hsp90·FKBP52·dyenin complex may be responsible for the retrotransport of MR; (b) a differential recruitment of TPR proteins such as FKBP51, FKBP52, and PP5 takes place during the early steps of hormone-dependent activation of the receptor; (c) importantly, this swapping of TPR proteins depends on the nature of the ligand; and (d) inasmuch as FKBP51 also showed an inhibitory effect on MR-dependent transcription, it should be dissociated from the MR·Hsp90 complex to positively regulate the mineralocorticoid effect.
Fil: Gallo, Luciana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina
Fil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina
Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina - Materia
-
Hsp90
Mineralocorticoid Receptor
Immunophilins - 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:11336/30527
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oai:ri.conicet.gov.ar:11336/30527 |
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3498 |
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CONICET Digital (CONICET) |
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Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional ActivityGallo, Luciana InesGhini, Alberto AntonioPiwien Pilipuk, GracielaGaligniana, Mario DanielHsp90Mineralocorticoid ReceptorImmunophilinshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The mineralocorticoid receptor (MR) forms oligomers with the heat-shock protein 90 (Hsp90) -based heterocomplex, which contains tetratricopeptide repeat (TPR) domain immunophilins (IMMs). Here we investigated the unknown biological role of IMMs in the MR·Hsp90 complex. Upon hormone binding, FKBP52 was greatly recruited to MR·Hsp90 complexes along with dynein motors, whereas FKBP51 was dissociated. Importantly, the Hsp90 inhibitor geldanamycin impaired the retrograde transport of MR, suggesting that the Hsp90·IMM·dynein molecular machinery is required for MR movement. To elucidate the mechanism of action of MR, the synthetic ligand 11,19-oxidoprogesterone was used as a tool. This steroid showed equivalent agonistic potency to natural agonists and was able to potentiate their mineralocorticoid action. Importantly, aldosterone binding recruited greater amounts of FKBP52 and dynein than 11,19-oxidoprogesterone binding to MR. Interestingly, 11,19-oxidoprogesterone binding also favored the selective recruitment of the IMM-like Ser/Thr phosphatase PP5. Each hormone/MR complex yielded different proteolytic peptide patterns, suggesting that MR acquires different conformations upon steroid binding. Also, hormone/MR complexes showed different nuclear translocation rates and subnuclear redistribution. All these observations may be related to the selective swapping of associated factors. We conclude that (a) the Hsp90·FKBP52·dyenin complex may be responsible for the retrotransport of MR; (b) a differential recruitment of TPR proteins such as FKBP51, FKBP52, and PP5 takes place during the early steps of hormone-dependent activation of the receptor; (c) importantly, this swapping of TPR proteins depends on the nature of the ligand; and (d) inasmuch as FKBP51 also showed an inhibitory effect on MR-dependent transcription, it should be dissociated from the MR·Hsp90 complex to positively regulate the mineralocorticoid effect.Fil: Gallo, Luciana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; ArgentinaFil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaAmerican Chemical Society2007-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/30527Gallo, Luciana Ines; Ghini, Alberto Antonio; Piwien Pilipuk, Graciela; Galigniana, Mario Daniel; Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity; American Chemical Society; Biochemistry; 46; 49; 11-2007; 14044-140570006-2960CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/bi701372cinfo:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/bi701372cinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:58:03Zoai:ri.conicet.gov.ar:11336/30527instacron: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:34982025-09-03 09:58:03.588CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
title |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
spellingShingle |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity Gallo, Luciana Ines Hsp90 Mineralocorticoid Receptor Immunophilins |
title_short |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
title_full |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
title_fullStr |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
title_full_unstemmed |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
title_sort |
Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity |
dc.creator.none.fl_str_mv |
Gallo, Luciana Ines Ghini, Alberto Antonio Piwien Pilipuk, Graciela Galigniana, Mario Daniel |
author |
Gallo, Luciana Ines |
author_facet |
Gallo, Luciana Ines Ghini, Alberto Antonio Piwien Pilipuk, Graciela Galigniana, Mario Daniel |
author_role |
author |
author2 |
Ghini, Alberto Antonio Piwien Pilipuk, Graciela Galigniana, Mario Daniel |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Hsp90 Mineralocorticoid Receptor Immunophilins |
topic |
Hsp90 Mineralocorticoid Receptor Immunophilins |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
The mineralocorticoid receptor (MR) forms oligomers with the heat-shock protein 90 (Hsp90) -based heterocomplex, which contains tetratricopeptide repeat (TPR) domain immunophilins (IMMs). Here we investigated the unknown biological role of IMMs in the MR·Hsp90 complex. Upon hormone binding, FKBP52 was greatly recruited to MR·Hsp90 complexes along with dynein motors, whereas FKBP51 was dissociated. Importantly, the Hsp90 inhibitor geldanamycin impaired the retrograde transport of MR, suggesting that the Hsp90·IMM·dynein molecular machinery is required for MR movement. To elucidate the mechanism of action of MR, the synthetic ligand 11,19-oxidoprogesterone was used as a tool. This steroid showed equivalent agonistic potency to natural agonists and was able to potentiate their mineralocorticoid action. Importantly, aldosterone binding recruited greater amounts of FKBP52 and dynein than 11,19-oxidoprogesterone binding to MR. Interestingly, 11,19-oxidoprogesterone binding also favored the selective recruitment of the IMM-like Ser/Thr phosphatase PP5. Each hormone/MR complex yielded different proteolytic peptide patterns, suggesting that MR acquires different conformations upon steroid binding. Also, hormone/MR complexes showed different nuclear translocation rates and subnuclear redistribution. All these observations may be related to the selective swapping of associated factors. We conclude that (a) the Hsp90·FKBP52·dyenin complex may be responsible for the retrotransport of MR; (b) a differential recruitment of TPR proteins such as FKBP51, FKBP52, and PP5 takes place during the early steps of hormone-dependent activation of the receptor; (c) importantly, this swapping of TPR proteins depends on the nature of the ligand; and (d) inasmuch as FKBP51 also showed an inhibitory effect on MR-dependent transcription, it should be dissociated from the MR·Hsp90 complex to positively regulate the mineralocorticoid effect. Fil: Gallo, Luciana Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Ghini, Alberto Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina Fil: Piwien Pilipuk, Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Galigniana, Mario Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina |
description |
The mineralocorticoid receptor (MR) forms oligomers with the heat-shock protein 90 (Hsp90) -based heterocomplex, which contains tetratricopeptide repeat (TPR) domain immunophilins (IMMs). Here we investigated the unknown biological role of IMMs in the MR·Hsp90 complex. Upon hormone binding, FKBP52 was greatly recruited to MR·Hsp90 complexes along with dynein motors, whereas FKBP51 was dissociated. Importantly, the Hsp90 inhibitor geldanamycin impaired the retrograde transport of MR, suggesting that the Hsp90·IMM·dynein molecular machinery is required for MR movement. To elucidate the mechanism of action of MR, the synthetic ligand 11,19-oxidoprogesterone was used as a tool. This steroid showed equivalent agonistic potency to natural agonists and was able to potentiate their mineralocorticoid action. Importantly, aldosterone binding recruited greater amounts of FKBP52 and dynein than 11,19-oxidoprogesterone binding to MR. Interestingly, 11,19-oxidoprogesterone binding also favored the selective recruitment of the IMM-like Ser/Thr phosphatase PP5. Each hormone/MR complex yielded different proteolytic peptide patterns, suggesting that MR acquires different conformations upon steroid binding. Also, hormone/MR complexes showed different nuclear translocation rates and subnuclear redistribution. All these observations may be related to the selective swapping of associated factors. We conclude that (a) the Hsp90·FKBP52·dyenin complex may be responsible for the retrotransport of MR; (b) a differential recruitment of TPR proteins such as FKBP51, FKBP52, and PP5 takes place during the early steps of hormone-dependent activation of the receptor; (c) importantly, this swapping of TPR proteins depends on the nature of the ligand; and (d) inasmuch as FKBP51 also showed an inhibitory effect on MR-dependent transcription, it should be dissociated from the MR·Hsp90 complex to positively regulate the mineralocorticoid effect. |
publishDate |
2007 |
dc.date.none.fl_str_mv |
2007-11 |
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/11336/30527 Gallo, Luciana Ines; Ghini, Alberto Antonio; Piwien Pilipuk, Graciela; Galigniana, Mario Daniel; Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity; American Chemical Society; Biochemistry; 46; 49; 11-2007; 14044-14057 0006-2960 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/30527 |
identifier_str_mv |
Gallo, Luciana Ines; Ghini, Alberto Antonio; Piwien Pilipuk, Graciela; Galigniana, Mario Daniel; Differential Recruitment of Tetratricorpeptide Repeat Domain Immunophilins to the Mineralocorticoid Receptor Influences both Heat-Shock Protein 90-Dependent Retrotransport and Hormone-Dependent Transcriptional Activity; American Chemical Society; Biochemistry; 46; 49; 11-2007; 14044-14057 0006-2960 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1021/bi701372c info:eu-repo/semantics/altIdentifier/url/http://pubs.acs.org/doi/abs/10.1021/bi701372c |
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 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 |
_version_ |
1842269498140262400 |
score |
13.13397 |