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Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence
Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
D.A. Spandidos
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551412/ https://www.ncbi.nlm.nih.gov/pubmed/36169180 http://dx.doi.org/10.3892/mmr.2022.12861 |
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author | Rodríguez, Sergio Bermúdez, Litzy Gisella González, Daniel Bernal, Camila Cañas, Alejandra Morales-Ruíz, Teresa Henríquez, Berta Rojas, Adriana |
author_facet | Rodríguez, Sergio Bermúdez, Litzy Gisella González, Daniel Bernal, Camila Cañas, Alejandra Morales-Ruíz, Teresa Henríquez, Berta Rojas, Adriana |
author_sort | Rodríguez, Sergio |
collection | PubMed |
description | Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16(INK4A) protein is a key regulator of this process via its cyclin-dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD(+))-dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non-senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl-transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene. |
format | Online Article Text |
id | pubmed-9551412 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | D.A. Spandidos |
record_format | MEDLINE/PubMed |
spelling | pubmed-95514122022-10-15 Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence Rodríguez, Sergio Bermúdez, Litzy Gisella González, Daniel Bernal, Camila Cañas, Alejandra Morales-Ruíz, Teresa Henríquez, Berta Rojas, Adriana Mol Med Rep Articles Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16(INK4A) protein is a key regulator of this process via its cyclin-dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD(+))-dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non-senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl-transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene. D.A. Spandidos 2022-09-27 /pmc/articles/PMC9551412/ /pubmed/36169180 http://dx.doi.org/10.3892/mmr.2022.12861 Text en Copyright: © Rodríguez et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. |
spellingShingle | Articles Rodríguez, Sergio Bermúdez, Litzy Gisella González, Daniel Bernal, Camila Cañas, Alejandra Morales-Ruíz, Teresa Henríquez, Berta Rojas, Adriana Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence |
title | Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence |
title_full | Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence |
title_fullStr | Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence |
title_full_unstemmed | Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence |
title_short | Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence |
title_sort | transcriptional regulation of cdkn2a/p16 by sirtuin 7 in senescence |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9551412/ https://www.ncbi.nlm.nih.gov/pubmed/36169180 http://dx.doi.org/10.3892/mmr.2022.12861 |
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