RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity

Autores
Druker, Jimena Paola; Liberman, Ana Clara; Antunica Noguerol, María de Las Nieves; Gerez, Juan Atilio; Paez Pereda, Marcelo; Rein, Theo; Iñiguez Lluhi, Jorge A.; Holsboer, Florian; Arzt, Eduardo Simon
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation.We nowdemonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulatesGRtranscriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating thatGRSUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-inducedGRSUMOylation. These results show that inhibitory and stimulatorySUMOsites are present in theGRand at higher SUMOylation levels the stimulatory one becomes dominant.
Fil: Druker, Jimena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Paez Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania
Fil: Rein, Theo. Max Planck Institute of Psychiatry; Alemania
Fil: Iñiguez Lluhi, Jorge A.. University of Michigan Medical School. Department of Pharmacology; Estados Unidos
Fil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Materia
Rsume
Gr
Sumoylation
Sumo
Heat-Shock
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:11336/3103
Acceder
id CONICETDig_dcda15107bf8e0dc5161147a8266572e
oai_identifier_str oai:ri.conicet.gov.ar:11336/3103
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activityDruker, Jimena PaolaLiberman, Ana ClaraAntunica Noguerol, María de Las NievesGerez, Juan AtilioPaez Pereda, MarceloRein, TheoIñiguez Lluhi, Jorge A.Holsboer, FlorianArzt, Eduardo SimonRsumeGrSumoylationSumoHeat-Shockhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation.We nowdemonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulatesGRtranscriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating thatGRSUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-inducedGRSUMOylation. These results show that inhibitory and stimulatorySUMOsites are present in theGRand at higher SUMOylation levels the stimulatory one becomes dominant.Fil: Druker, Jimena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaFil: Paez Pereda, Marcelo. Max Planck Institute of Psychiatry; AlemaniaFil: Rein, Theo. Max Planck Institute of Psychiatry; AlemaniaFil: Iñiguez Lluhi, Jorge A.. University of Michigan Medical School. Department of Pharmacology; Estados UnidosFil: Holsboer, Florian. Max Planck Institute of Psychiatry; AlemaniaFil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; ArgentinaAmerican Society for Microbiology2013-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3103Druker, Jimena Paola; Liberman, Ana Clara; Antunica Noguerol, María de Las Nieves; Gerez, Juan Atilio; Paez Pereda, Marcelo; et al.; RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity; American Society for Microbiology; Molecular and Cellular Biology; 33; 11; 6-2013; 2116-21270270-7306enginfo:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1128/MCB.01470-12info:eu-repo/semantics/altIdentifier/doi/10.1128%2FMCB.01470-12info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:19:26Zoai:ri.conicet.gov.ar:11336/3103instacron: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:34982025-10-22 12:19:27.051CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
spellingShingle RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
Druker, Jimena Paola
Rsume
Gr
Sumoylation
Sumo
Heat-Shock
title_short RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_full RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_fullStr RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_full_unstemmed RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
title_sort RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity
dc.creator.none.fl_str_mv Druker, Jimena Paola
Liberman, Ana Clara
Antunica Noguerol, María de Las Nieves
Gerez, Juan Atilio
Paez Pereda, Marcelo
Rein, Theo
Iñiguez Lluhi, Jorge A.
Holsboer, Florian
Arzt, Eduardo Simon
author Druker, Jimena Paola
author_facet Druker, Jimena Paola
Liberman, Ana Clara
Antunica Noguerol, María de Las Nieves
Gerez, Juan Atilio
Paez Pereda, Marcelo
Rein, Theo
Iñiguez Lluhi, Jorge A.
Holsboer, Florian
Arzt, Eduardo Simon
author_role author
author2 Liberman, Ana Clara
Antunica Noguerol, María de Las Nieves
Gerez, Juan Atilio
Paez Pereda, Marcelo
Rein, Theo
Iñiguez Lluhi, Jorge A.
Holsboer, Florian
Arzt, Eduardo Simon
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Rsume
Gr
Sumoylation
Sumo
Heat-Shock
topic Rsume
Gr
Sumoylation
Sumo
Heat-Shock
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation.We nowdemonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulatesGRtranscriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating thatGRSUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-inducedGRSUMOylation. These results show that inhibitory and stimulatorySUMOsites are present in theGRand at higher SUMOylation levels the stimulatory one becomes dominant.
Fil: Druker, Jimena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Liberman, Ana Clara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Antunica Noguerol, María de Las Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Gerez, Juan Atilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
Fil: Paez Pereda, Marcelo. Max Planck Institute of Psychiatry; Alemania
Fil: Rein, Theo. Max Planck Institute of Psychiatry; Alemania
Fil: Iñiguez Lluhi, Jorge A.. University of Michigan Medical School. Department of Pharmacology; Estados Unidos
Fil: Holsboer, Florian. Max Planck Institute of Psychiatry; Alemania
Fil: Arzt, Eduardo Simon. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires; Argentina
description Glucocorticoid receptor (GR) activity is modulated by posttranslational modifications, including phosphorylation, ubiquitination, and SUMOylation. The GR has three SUMOylation sites: lysine 297 (K297) and K313 in the N-terminal domain (NTD) and K721 within the ligand-binding domain. SUMOylation of the NTD sites mediates the negative effect of the synergy control motifs of GR on promoters with closely spaced GR binding sites. There is scarce evidence on the role of SUMO conjugation to K721 and its impact on GR transcriptional activity. We have previously shown that RSUME (RWD-containing SUMOylation enhancer) increases protein SUMOylation.We nowdemonstrate that RSUME interacts with the GR and increases its SUMOylation. RSUME regulatesGRtranscriptional activity and the expression of its endogenous target genes, FKBP51 and S100P. RSUME uncovers a positive role for the third SUMOylation site, K721, on GR-mediated transcription, demonstrating thatGRSUMOylation acts positively in the presence of a SUMOylation enhancer. Both mutation of K721 and small interfering RNA-mediated RSUME knockdown diminish GRIP1 coactivator activity. RSUME, whose expression is induced under stress conditions, is a key factor in heat shock-inducedGRSUMOylation. These results show that inhibitory and stimulatorySUMOsites are present in theGRand at higher SUMOylation levels the stimulatory one becomes dominant.
publishDate 2013
dc.date.none.fl_str_mv 2013-06
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/11336/3103
Druker, Jimena Paola; Liberman, Ana Clara; Antunica Noguerol, María de Las Nieves; Gerez, Juan Atilio; Paez Pereda, Marcelo; et al.; RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity; American Society for Microbiology; Molecular and Cellular Biology; 33; 11; 6-2013; 2116-2127
0270-7306
url http://hdl.handle.net/11336/3103
identifier_str_mv Druker, Jimena Paola; Liberman, Ana Clara; Antunica Noguerol, María de Las Nieves; Gerez, Juan Atilio; Paez Pereda, Marcelo; et al.; RSUME enhances glucocorticoid receptor SUMOylation and transcriptional activity; American Society for Microbiology; Molecular and Cellular Biology; 33; 11; 6-2013; 2116-2127
0270-7306
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.tandfonline.com/doi/full/10.1128/MCB.01470-12
info:eu-repo/semantics/altIdentifier/doi/10.1128%2FMCB.01470-12
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
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
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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score 12.982451

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