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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/3103
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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 Técnicas2025-09-29T10:46:04Zoai: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:34982025-09-29 10:46:04.914CONICET 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 |
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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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1844614501592203264 |
score |
13.070432 |