p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation
- Autores
- Sonzogni, Silvina Veronica; Ogara, Maria Florencia; Belluscio, Laura María; Castillo, Daniela Susana; Scassa, Maria Elida; Canepa, Eduardo Tomas
- Año de publicación
- 2014
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Background: During evolution, organisms with renewable tissues have developed mechanisms to prevent tumorigenesis, including cellular senescence and apoptosis. Cellular senescence is characterized by a permanent cell cycle arrest triggered by both endogenous stress and exogenous stress. The p19INK4d, a member of the family of cyclin-dependent kinase inhibitors (INK4), plays an important role on cell cycle regulation and in the cellular DNA damage response. We hypothesize that p19INK4d is a potential factor involved in the onset and/or maintenance of the senescent state. Methods: Senescence was confirmed by measuring the cell cycle arrest and the senescence-associated β-galactosidase activity. Changes in p19INK4d expression and localization during senescence were determined by Western blot and immunofluorescence assays. Chromatin condensation was measured by microccocal nuclease digestion and histone salt extraction. Results: The data presented here show for the first time that p19INK4d expression is up-regulated by different types of senescence. Changes in senescence-associated hallmarks were driven by modulation of p19 expression indicating a direct link between p19INK4d induction and the establishment of cellular senescence. Following a senescence stimulus, p19INK4d translocates to the nucleus and tightly associates with chromatin. Moreover, reduced levels of p19INK4d impair senescence-related global genomic heterochromatinization. Analysis of p19INK4d mRNA and protein levels in tissues from differently aged mice revealed an up-regulation of p19INK4d that correlates with age. Conclusion: We propose that p19INK4d participates in the cellular mechanisms that trigger senescence by contributing to chromatin compaction. General significance: This study provides novel insights into the dynamics process of cellular senescence, a central tumor suppressive mechanism.
Fil: Sonzogni, Silvina Veronica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ogara, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Belluscio, Laura María. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Castillo, Daniela Susana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Scassa, Maria Elida. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Canepa, Eduardo Tomas. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina - Materia
-
Cellular Senescence
Cdk Inhibitor
Dna Damage
Heterochromatin
Aging - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/32194
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p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formationSonzogni, Silvina VeronicaOgara, Maria FlorenciaBelluscio, Laura MaríaCastillo, Daniela SusanaScassa, Maria ElidaCanepa, Eduardo TomasCellular SenescenceCdk InhibitorDna DamageHeterochromatinAginghttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Background: During evolution, organisms with renewable tissues have developed mechanisms to prevent tumorigenesis, including cellular senescence and apoptosis. Cellular senescence is characterized by a permanent cell cycle arrest triggered by both endogenous stress and exogenous stress. The p19INK4d, a member of the family of cyclin-dependent kinase inhibitors (INK4), plays an important role on cell cycle regulation and in the cellular DNA damage response. We hypothesize that p19INK4d is a potential factor involved in the onset and/or maintenance of the senescent state. Methods: Senescence was confirmed by measuring the cell cycle arrest and the senescence-associated β-galactosidase activity. Changes in p19INK4d expression and localization during senescence were determined by Western blot and immunofluorescence assays. Chromatin condensation was measured by microccocal nuclease digestion and histone salt extraction. Results: The data presented here show for the first time that p19INK4d expression is up-regulated by different types of senescence. Changes in senescence-associated hallmarks were driven by modulation of p19 expression indicating a direct link between p19INK4d induction and the establishment of cellular senescence. Following a senescence stimulus, p19INK4d translocates to the nucleus and tightly associates with chromatin. Moreover, reduced levels of p19INK4d impair senescence-related global genomic heterochromatinization. Analysis of p19INK4d mRNA and protein levels in tissues from differently aged mice revealed an up-regulation of p19INK4d that correlates with age. Conclusion: We propose that p19INK4d participates in the cellular mechanisms that trigger senescence by contributing to chromatin compaction. General significance: This study provides novel insights into the dynamics process of cellular senescence, a central tumor suppressive mechanism.Fil: Sonzogni, Silvina Veronica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ogara, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Belluscio, Laura María. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Castillo, Daniela Susana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scassa, Maria Elida. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Canepa, Eduardo Tomas. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2014-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/32194Canepa, Eduardo Tomas; Scassa, Maria Elida; Castillo, Daniela Susana; Belluscio, Laura María; Ogara, Maria Florencia; Sonzogni, Silvina Veronica; et al.; p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1840; 7; 3-2014; 2171-21830304-4165CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416514001196info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2014.03.015info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:20Zoai:ri.conicet.gov.ar:11336/32194instacron: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 09:43:20.429CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
title |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
spellingShingle |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation Sonzogni, Silvina Veronica Cellular Senescence Cdk Inhibitor Dna Damage Heterochromatin Aging |
title_short |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
title_full |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
title_fullStr |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
title_full_unstemmed |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
title_sort |
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation |
dc.creator.none.fl_str_mv |
Sonzogni, Silvina Veronica Ogara, Maria Florencia Belluscio, Laura María Castillo, Daniela Susana Scassa, Maria Elida Canepa, Eduardo Tomas |
author |
Sonzogni, Silvina Veronica |
author_facet |
Sonzogni, Silvina Veronica Ogara, Maria Florencia Belluscio, Laura María Castillo, Daniela Susana Scassa, Maria Elida Canepa, Eduardo Tomas |
author_role |
author |
author2 |
Ogara, Maria Florencia Belluscio, Laura María Castillo, Daniela Susana Scassa, Maria Elida Canepa, Eduardo Tomas |
author2_role |
author author author author author |
dc.subject.none.fl_str_mv |
Cellular Senescence Cdk Inhibitor Dna Damage Heterochromatin Aging |
topic |
Cellular Senescence Cdk Inhibitor Dna Damage Heterochromatin Aging |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Background: During evolution, organisms with renewable tissues have developed mechanisms to prevent tumorigenesis, including cellular senescence and apoptosis. Cellular senescence is characterized by a permanent cell cycle arrest triggered by both endogenous stress and exogenous stress. The p19INK4d, a member of the family of cyclin-dependent kinase inhibitors (INK4), plays an important role on cell cycle regulation and in the cellular DNA damage response. We hypothesize that p19INK4d is a potential factor involved in the onset and/or maintenance of the senescent state. Methods: Senescence was confirmed by measuring the cell cycle arrest and the senescence-associated β-galactosidase activity. Changes in p19INK4d expression and localization during senescence were determined by Western blot and immunofluorescence assays. Chromatin condensation was measured by microccocal nuclease digestion and histone salt extraction. Results: The data presented here show for the first time that p19INK4d expression is up-regulated by different types of senescence. Changes in senescence-associated hallmarks were driven by modulation of p19 expression indicating a direct link between p19INK4d induction and the establishment of cellular senescence. Following a senescence stimulus, p19INK4d translocates to the nucleus and tightly associates with chromatin. Moreover, reduced levels of p19INK4d impair senescence-related global genomic heterochromatinization. Analysis of p19INK4d mRNA and protein levels in tissues from differently aged mice revealed an up-regulation of p19INK4d that correlates with age. Conclusion: We propose that p19INK4d participates in the cellular mechanisms that trigger senescence by contributing to chromatin compaction. General significance: This study provides novel insights into the dynamics process of cellular senescence, a central tumor suppressive mechanism. Fil: Sonzogni, Silvina Veronica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Ogara, Maria Florencia. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Belluscio, Laura María. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Castillo, Daniela Susana. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Scassa, Maria Elida. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Canepa, Eduardo Tomas. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
description |
Background: During evolution, organisms with renewable tissues have developed mechanisms to prevent tumorigenesis, including cellular senescence and apoptosis. Cellular senescence is characterized by a permanent cell cycle arrest triggered by both endogenous stress and exogenous stress. The p19INK4d, a member of the family of cyclin-dependent kinase inhibitors (INK4), plays an important role on cell cycle regulation and in the cellular DNA damage response. We hypothesize that p19INK4d is a potential factor involved in the onset and/or maintenance of the senescent state. Methods: Senescence was confirmed by measuring the cell cycle arrest and the senescence-associated β-galactosidase activity. Changes in p19INK4d expression and localization during senescence were determined by Western blot and immunofluorescence assays. Chromatin condensation was measured by microccocal nuclease digestion and histone salt extraction. Results: The data presented here show for the first time that p19INK4d expression is up-regulated by different types of senescence. Changes in senescence-associated hallmarks were driven by modulation of p19 expression indicating a direct link between p19INK4d induction and the establishment of cellular senescence. Following a senescence stimulus, p19INK4d translocates to the nucleus and tightly associates with chromatin. Moreover, reduced levels of p19INK4d impair senescence-related global genomic heterochromatinization. Analysis of p19INK4d mRNA and protein levels in tissues from differently aged mice revealed an up-regulation of p19INK4d that correlates with age. Conclusion: We propose that p19INK4d participates in the cellular mechanisms that trigger senescence by contributing to chromatin compaction. General significance: This study provides novel insights into the dynamics process of cellular senescence, a central tumor suppressive mechanism. |
publishDate |
2014 |
dc.date.none.fl_str_mv |
2014-03 |
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/11336/32194 Canepa, Eduardo Tomas; Scassa, Maria Elida; Castillo, Daniela Susana; Belluscio, Laura María; Ogara, Maria Florencia; Sonzogni, Silvina Veronica; et al.; p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1840; 7; 3-2014; 2171-2183 0304-4165 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/32194 |
identifier_str_mv |
Canepa, Eduardo Tomas; Scassa, Maria Elida; Castillo, Daniela Susana; Belluscio, Laura María; Ogara, Maria Florencia; Sonzogni, Silvina Veronica; et al.; p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation; Elsevier Science; Biochimica et Biophysica Acta- General Subjects; 1840; 7; 3-2014; 2171-2183 0304-4165 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.sciencedirect.com/science/article/pii/S0304416514001196 info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2014.03.015 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier Science |
publisher.none.fl_str_mv |
Elsevier Science |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
CONICET Digital (CONICET) |
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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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1844613363847397376 |
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13.070432 |