Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.

[EN]Cellular senescence is a cell fate response characterized by a permanent cell cycle arrest driven primarily the by cell cycle inhibitor and tumor suppressor proteins p16Ink4a and p21Cip1/Waf1. In mice, the p21Cip1/Waf1 encoding locus, Cdkn1a, is known to generate two transcripts that produce ide...

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Authors: López Domínguez, José Alberto, Rodríguez-López, Sandra, Ahumada-Castro, Ulises, Desprez, Pierre-Yves, Konovalenko, Maria, Laberge, Remi-Martin, Cárdenas, César, Villalba, José Manuel, Campisi, Judith
Format: article
Status:Published version
Publication Date:2021
Country:España
Institution:Universidad de Salamanca (USAL)
Repository:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/166749
Online Access:http://hdl.handle.net/10366/166749
Access Level:Open access
Keyword:Aging
Cellular senescence
Biomarker
Chemotherapy
Senolysis
2302 Bioquímica
2407 Biología Celular
id ES_3200fbeabcd69cce71f3e11e42584d49
oai_identifier_str oai:gredos.usal.es:10366/166749
network_acronym_str ES
network_name_str España
repository_id_str
spelling Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.López Domínguez, José AlbertoRodríguez-López, SandraAhumada-Castro, UlisesDesprez, Pierre-YvesKonovalenko, MariaLaberge, Remi-MartinCárdenas, CésarVillalba, José ManuelCampisi, JudithAgingCellular senescenceBiomarkerChemotherapySenolysis2302 Bioquímica2407 Biología Celular[EN]Cellular senescence is a cell fate response characterized by a permanent cell cycle arrest driven primarily the by cell cycle inhibitor and tumor suppressor proteins p16Ink4a and p21Cip1/Waf1. In mice, the p21Cip1/Waf1 encoding locus, Cdkn1a, is known to generate two transcripts that produce identical proteins, but one of these transcript variants is poorly characterized. We show that the Cdkn1a transcript variant 2, but not the better-studied variant 1, is selectively elevated during natural aging across multiple mouse tissues. Importantly, mouse cells induced to senescence in culture by genotoxic stress (ionizing radiation or doxorubicin) upregulated both transcripts, but with different temporal dynamics: variant 1 responded nearly immediately to genotoxic stress, whereas variant 2 increased much more slowly as cells acquired senescent characteristics. Upon treating mice systemically with doxorubicin, which induces widespread cellular senescence in vivo, variant 2 increased to a larger extent than variant 1. Variant 2 levels were also more sensitive to the senolytic drug ABT-263 in naturally aged mice. Thus, variant 2 is a novel and more sensitive marker than variant 1 or total p21Cip1/Waf1 protein for assessing the senescent cell burden and clearance in mice.202520252021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10366/166749reponame:GREDOS. Repositorio Institucional de la Universidad de Salamancainstname:Universidad de Salamanca (USAL)InglésBFU2015-64630-RAttribution-NonCommercial-NoDerivs 3.0 Unportedhttp://creativecommons.org/licenses/by-nc-nd/3.0/info:eu-repo/semantics/openAccessoai:gredos.usal.es:10366/1667492026-06-07T06:28:51Z
dc.title.none.fl_str_mv Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
title Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
spellingShingle Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
López Domínguez, José Alberto
Aging
Cellular senescence
Biomarker
Chemotherapy
Senolysis
2302 Bioquímica
2407 Biología Celular
title_short Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
title_full Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
title_fullStr Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
title_full_unstemmed Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
title_sort Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.
dc.creator.none.fl_str_mv López Domínguez, José Alberto
Rodríguez-López, Sandra
Ahumada-Castro, Ulises
Desprez, Pierre-Yves
Konovalenko, Maria
Laberge, Remi-Martin
Cárdenas, César
Villalba, José Manuel
Campisi, Judith
author López Domínguez, José Alberto
author_facet López Domínguez, José Alberto
Rodríguez-López, Sandra
Ahumada-Castro, Ulises
Desprez, Pierre-Yves
Konovalenko, Maria
Laberge, Remi-Martin
Cárdenas, César
Villalba, José Manuel
Campisi, Judith
author_role author
author2 Rodríguez-López, Sandra
Ahumada-Castro, Ulises
Desprez, Pierre-Yves
Konovalenko, Maria
Laberge, Remi-Martin
Cárdenas, César
Villalba, José Manuel
Campisi, Judith
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Aging
Cellular senescence
Biomarker
Chemotherapy
Senolysis
2302 Bioquímica
2407 Biología Celular
topic Aging
Cellular senescence
Biomarker
Chemotherapy
Senolysis
2302 Bioquímica
2407 Biología Celular
description [EN]Cellular senescence is a cell fate response characterized by a permanent cell cycle arrest driven primarily the by cell cycle inhibitor and tumor suppressor proteins p16Ink4a and p21Cip1/Waf1. In mice, the p21Cip1/Waf1 encoding locus, Cdkn1a, is known to generate two transcripts that produce identical proteins, but one of these transcript variants is poorly characterized. We show that the Cdkn1a transcript variant 2, but not the better-studied variant 1, is selectively elevated during natural aging across multiple mouse tissues. Importantly, mouse cells induced to senescence in culture by genotoxic stress (ionizing radiation or doxorubicin) upregulated both transcripts, but with different temporal dynamics: variant 1 responded nearly immediately to genotoxic stress, whereas variant 2 increased much more slowly as cells acquired senescent characteristics. Upon treating mice systemically with doxorubicin, which induces widespread cellular senescence in vivo, variant 2 increased to a larger extent than variant 1. Variant 2 levels were also more sensitive to the senolytic drug ABT-263 in naturally aged mice. Thus, variant 2 is a novel and more sensitive marker than variant 1 or total p21Cip1/Waf1 protein for assessing the senescent cell burden and clearance in mice.
publishDate 2021
dc.date.none.fl_str_mv 2021
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10366/166749
url http://hdl.handle.net/10366/166749
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv BFU2015-64630-R
dc.rights.none.fl_str_mv Attribution-NonCommercial-NoDerivs 3.0 Unported
http://creativecommons.org/licenses/by-nc-nd/3.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution-NonCommercial-NoDerivs 3.0 Unported
http://creativecommons.org/licenses/by-nc-nd/3.0/
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv reponame:GREDOS. Repositorio Institucional de la Universidad de Salamanca
instname:Universidad de Salamanca (USAL)
instname_str Universidad de Salamanca (USAL)
reponame_str GREDOS. Repositorio Institucional de la Universidad de Salamanca
collection GREDOS. Repositorio Institucional de la Universidad de Salamanca
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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