RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging
- Autores
- Fernández Larrosa, Pablo Nicolás; Ruiz Grecco, Marina; Mengual Gómez, Diego Luis; Alvarado, Cecilia Viviana; Panelo, Laura Carolina; Rubio, Maria Fernanda; Alonso, Daniel Fernando; Gomez, Daniel Eduardo; Costas, Monica Alejandra
- Año de publicación
- 2015
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenicfunctions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor ofapoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. Inthis work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cellsinhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition ofautophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization ofboth the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found thatRAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited bydepletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated inthe liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescentcell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence ofhuman fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstratethat RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressormechanism, avoiding the clonal expansion of risky old cells having damaged DNA.
Fil: Fernández Larrosa, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Ruiz Grecco, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Mengual Gómez, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Alvarado, Cecilia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Panelo, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Rubio, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina
Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina
Fil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina - Materia
-
NUCLEAR RECEPTOR COACTIVATOR
RAC3
AIB1
SENESCENCE - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/43537
Ver los metadatos del registro completo
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RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in agingFernández Larrosa, Pablo NicolásRuiz Grecco, MarinaMengual Gómez, Diego LuisAlvarado, Cecilia VivianaPanelo, Laura CarolinaRubio, Maria FernandaAlonso, Daniel FernandoGomez, Daniel EduardoCostas, Monica AlejandraNUCLEAR RECEPTOR COACTIVATORRAC3AIB1SENESCENCEhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenicfunctions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor ofapoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. Inthis work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cellsinhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition ofautophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization ofboth the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found thatRAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited bydepletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated inthe liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescentcell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence ofhuman fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstratethat RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressormechanism, avoiding the clonal expansion of risky old cells having damaged DNA.Fil: Fernández Larrosa, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Ruiz Grecco, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Mengual Gómez, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Alvarado, Cecilia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Panelo, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Rubio, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; ArgentinaFil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaNature Publishing Group2015-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/43537Fernández Larrosa, Pablo Nicolás; Ruiz Grecco, Marina; Mengual Gómez, Diego Luis; Alvarado, Cecilia Viviana; Panelo, Laura Carolina; et al.; RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging; Nature Publishing Group; Cell Death and Disease; 6; 10-2015; 1-12; e19021476-54032041-4889CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.nature.com/cddis/index.htmlinfo:eu-repo/semantics/altIdentifier/doi/10.1038/cddis.2015.218info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:39:03Zoai:ri.conicet.gov.ar:11336/43537instacron: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 10:39:03.883CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
title |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
spellingShingle |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging Fernández Larrosa, Pablo Nicolás NUCLEAR RECEPTOR COACTIVATOR RAC3 AIB1 SENESCENCE |
title_short |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
title_full |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
title_fullStr |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
title_full_unstemmed |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
title_sort |
RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging |
dc.creator.none.fl_str_mv |
Fernández Larrosa, Pablo Nicolás Ruiz Grecco, Marina Mengual Gómez, Diego Luis Alvarado, Cecilia Viviana Panelo, Laura Carolina Rubio, Maria Fernanda Alonso, Daniel Fernando Gomez, Daniel Eduardo Costas, Monica Alejandra |
author |
Fernández Larrosa, Pablo Nicolás |
author_facet |
Fernández Larrosa, Pablo Nicolás Ruiz Grecco, Marina Mengual Gómez, Diego Luis Alvarado, Cecilia Viviana Panelo, Laura Carolina Rubio, Maria Fernanda Alonso, Daniel Fernando Gomez, Daniel Eduardo Costas, Monica Alejandra |
author_role |
author |
author2 |
Ruiz Grecco, Marina Mengual Gómez, Diego Luis Alvarado, Cecilia Viviana Panelo, Laura Carolina Rubio, Maria Fernanda Alonso, Daniel Fernando Gomez, Daniel Eduardo Costas, Monica Alejandra |
author2_role |
author author author author author author author author |
dc.subject.none.fl_str_mv |
NUCLEAR RECEPTOR COACTIVATOR RAC3 AIB1 SENESCENCE |
topic |
NUCLEAR RECEPTOR COACTIVATOR RAC3 AIB1 SENESCENCE |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenicfunctions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor ofapoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. Inthis work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cellsinhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition ofautophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization ofboth the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found thatRAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited bydepletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated inthe liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescentcell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence ofhuman fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstratethat RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressormechanism, avoiding the clonal expansion of risky old cells having damaged DNA. Fil: Fernández Larrosa, Pablo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Ruiz Grecco, Marina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Mengual Gómez, Diego Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Alvarado, Cecilia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Panelo, Laura Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Rubio, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina Fil: Alonso, Daniel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Gomez, Daniel Eduardo. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnología. Laboratorio de Oncología Molecular; Argentina Fil: Costas, Monica Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentina |
description |
Receptor-associated coactivator 3 (RAC3) is a nuclear receptor coactivator usually overexpressed in tumors that exerts oncogenicfunctions in the cytoplasm and the nucleus. Although as part of its oncogenic actions it was previously identified as an inhibitor ofapoptosis and autophagy, its expression is required in order to preserve the pluripotency and embryonic stem cell self-renewal. Inthis work we investigated its role in cellular senescence. We found that RAC3 overexpression in the nontumoral HEK293 cellsinhibits the premature senescence induced by hydrogen peroxide or rapamycin. The mechanism involves not only the inhibition ofautophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization ofboth the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1. Furthermore, we found thatRAC3 overexpression is required in order to maintain the telomerase activity. In tumoral HeLa cells its activity was inhibited bydepletion of RAC3 inducing replicative senescence. Moreover, we demonstrated that in vivo, levels of RAC3 are downregulated inthe liver from aged as compared with young rats, whereas the levels of p21 are increased, correlating with the expected senescentcell contents in aged tissues. A similar downregulation of RAC3 was observed in the premature and replicative senescence ofhuman fetal WI-38 cells and premature senescence of hepatocyte HepG2 cell line. Taken together, all these results demonstratethat RAC3 is an inhibitor of senescence whose downregulation in aged individuals could be probably a tumor suppressormechanism, avoiding the clonal expansion of risky old cells having damaged DNA. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015-10 |
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/11336/43537 Fernández Larrosa, Pablo Nicolás; Ruiz Grecco, Marina; Mengual Gómez, Diego Luis; Alvarado, Cecilia Viviana; Panelo, Laura Carolina; et al.; RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging; Nature Publishing Group; Cell Death and Disease; 6; 10-2015; 1-12; e1902 1476-5403 2041-4889 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/43537 |
identifier_str_mv |
Fernández Larrosa, Pablo Nicolás; Ruiz Grecco, Marina; Mengual Gómez, Diego Luis; Alvarado, Cecilia Viviana; Panelo, Laura Carolina; et al.; RAC3 more than a nuclear receptor coactivator: A key inhibitor of senescence that is down-regulated in aging; Nature Publishing Group; Cell Death and Disease; 6; 10-2015; 1-12; e1902 1476-5403 2041-4889 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://www.nature.com/cddis/index.html info:eu-repo/semantics/altIdentifier/doi/10.1038/cddis.2015.218 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
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) |
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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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1844614415092023296 |
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13.070432 |