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dc.contributor.author
Sonzogni, Silvina Veronica
dc.contributor.author
Ogara, Maria Florencia
dc.contributor.author
Belluscio, Laura María
dc.contributor.author
Castillo, Daniela Susana
dc.contributor.author
Scassa, Maria Elida
dc.contributor.author
Canepa, Eduardo Tomas
dc.date.available
2018-01-03T19:06:14Z
dc.date.issued
2014-03
dc.identifier.citation
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
dc.identifier.issn
0304-4165
dc.identifier.uri
http://hdl.handle.net/11336/32194
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Science
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject
Cellular Senescence
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Cdk Inhibitor
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Dna Damage
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Heterochromatin
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Aging
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
p19INK4d is involved in the cellular senescence mechanism contributing to heterochromatin formation
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-12-29T17:32:21Z
dc.journal.volume
1840
dc.journal.number
7
dc.journal.pagination
2171-2183
dc.journal.pais
Países Bajos
dc.journal.ciudad
Amsterdam
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.description.fil
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
dc.journal.title
Biochimica et Biophysica Acta- General Subjects
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416514001196
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.bbagen.2014.03.015
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