p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.

Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the G(2)/M cell cycle arrest induced by DNA damage, but little is known about the role of this signaling pathway in the G(1)/S transition. Upregulation of the cyclin-dependent kinase inhibitor p21(Cip1) is thought t...

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Detalles Bibliográficos
Autores: Lafarga, Vanesa, Cuadrado, Ana, Lopez de Silanes, Isabel, Bengoechea, Rocio, Fernandez-Capetillo, Oscar, Nebreda, Angel R
Tipo de recurso: artículo
Fecha de publicación:2009
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/26088
Acceso en línea:https://hdl.handle.net/20.500.12105/26088
Access Level:acceso abierto
Palabra clave:DNA-DAMAGE
P21(WAF1/CIP1) EXPRESSION
DIFFERENTIAL ACTIVATION
ATAXIA-TELANGIECTASIA
UV-IRRADIATION
S-PHASE
PHOSPHORYLATION
p53
CELLS
INSTABILITY
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network_acronym_str ES
network_name_str España
repository_id_str
spelling p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.Lafarga, VanesaCuadrado, AnaLopez de Silanes, IsabelBengoechea, RocioFernandez-Capetillo, OscarNebreda, Angel RDNA-DAMAGEP21(WAF1/CIP1) EXPRESSIONDIFFERENTIAL ACTIVATIONATAXIA-TELANGIECTASIAUV-IRRADIATIONS-PHASEPHOSPHORYLATIONp53CELLSINSTABILITYActivation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the G(2)/M cell cycle arrest induced by DNA damage, but little is known about the role of this signaling pathway in the G(1)/S transition. Upregulation of the cyclin-dependent kinase inhibitor p21(Cip1) is thought to make a major contribution to the G(1)/S cell cycle arrest induced by gamma radiation. We show here that inhibition of p38 MAPK impairs p21(Cip1) accumulation and, as a result, the ability of cells to arrest in G(1) in response to gamma radiation. We found that p38 MAPK induces p21(Cip1) mRNA stabilization, without affecting its transcription or the stability of the protein. In particular, p38 MAPK phosphorylates the mRNA binding protein HuR on Thr118, which results in cytoplasmic accumulation of HuR and its enhanced binding to the p21(Cip1) mRNA. Our findings help to understand the emerging role of p38 MAPK in the cellular responses to DNA damage and reveal the existence of p53-independent networks that cooperate in modulating p21(Cip1) levels at the G(1)/S checkpoint.TAYLOR & FRANCIS INCFundacion Cientifica de la AECCMINISTERIO DE CIENCIA E INNOVACIÓN (ESPAÑA)Instituto de Salud Carlos III20252025-01-2120092009-08-0120092009-08-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12105/26088reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengMinisterio de Educación y Ciencia Not available BFU2007-60575 INTEGRACION DE SEÑALES POR P38 MAPK: FUNCIONES FISIOLOGICAS IN VIVO Y MECANISMOS DE REGULACION TUMORALopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/260882026-06-12T12:43:37Z
dc.title.none.fl_str_mv p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
title p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
spellingShingle p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
Lafarga, Vanesa
DNA-DAMAGE
P21(WAF1/CIP1) EXPRESSION
DIFFERENTIAL ACTIVATION
ATAXIA-TELANGIECTASIA
UV-IRRADIATION
S-PHASE
PHOSPHORYLATION
p53
CELLS
INSTABILITY
title_short p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
title_full p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
title_fullStr p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
title_full_unstemmed p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
title_sort p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
dc.creator.none.fl_str_mv Lafarga, Vanesa
Cuadrado, Ana
Lopez de Silanes, Isabel
Bengoechea, Rocio
Fernandez-Capetillo, Oscar
Nebreda, Angel R
author Lafarga, Vanesa
author_facet Lafarga, Vanesa
Cuadrado, Ana
Lopez de Silanes, Isabel
Bengoechea, Rocio
Fernandez-Capetillo, Oscar
Nebreda, Angel R
author_role author
author2 Cuadrado, Ana
Lopez de Silanes, Isabel
Bengoechea, Rocio
Fernandez-Capetillo, Oscar
Nebreda, Angel R
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Fundacion Cientifica de la AECC
MINISTERIO DE CIENCIA E INNOVACIÓN (ESPAÑA)
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv DNA-DAMAGE
P21(WAF1/CIP1) EXPRESSION
DIFFERENTIAL ACTIVATION
ATAXIA-TELANGIECTASIA
UV-IRRADIATION
S-PHASE
PHOSPHORYLATION
p53
CELLS
INSTABILITY
topic DNA-DAMAGE
P21(WAF1/CIP1) EXPRESSION
DIFFERENTIAL ACTIVATION
ATAXIA-TELANGIECTASIA
UV-IRRADIATION
S-PHASE
PHOSPHORYLATION
p53
CELLS
INSTABILITY
description Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the G(2)/M cell cycle arrest induced by DNA damage, but little is known about the role of this signaling pathway in the G(1)/S transition. Upregulation of the cyclin-dependent kinase inhibitor p21(Cip1) is thought to make a major contribution to the G(1)/S cell cycle arrest induced by gamma radiation. We show here that inhibition of p38 MAPK impairs p21(Cip1) accumulation and, as a result, the ability of cells to arrest in G(1) in response to gamma radiation. We found that p38 MAPK induces p21(Cip1) mRNA stabilization, without affecting its transcription or the stability of the protein. In particular, p38 MAPK phosphorylates the mRNA binding protein HuR on Thr118, which results in cytoplasmic accumulation of HuR and its enhanced binding to the p21(Cip1) mRNA. Our findings help to understand the emerging role of p38 MAPK in the cellular responses to DNA damage and reveal the existence of p53-independent networks that cooperate in modulating p21(Cip1) levels at the G(1)/S checkpoint.
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-08-01
2009
2009-08-01
2025
2025-01-21
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.12105/26088
url https://hdl.handle.net/20.500.12105/26088
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Ministerio de Educación y Ciencia Not available BFU2007-60575 INTEGRACION DE SEÑALES POR P38 MAPK: FUNCIONES FISIOLOGICAS IN VIVO Y MECANISMOS DE REGULACION TUMORAL
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 International
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv TAYLOR & FRANCIS INC
publisher.none.fl_str_mv TAYLOR & FRANCIS INC
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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