Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress

Reactive oxygen species (ROS) are an important source of cellular damage. When ROS intracellular levels increase, oxidative stress takes place affecting DNA stability and metabolic functions. To prevent these effects, stress-activated protein kinases (SAPKs) delay cell cycle progression and induce a...

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Autores: Cañete, Juan A., Andrés, Sonia, Muñoz Félix, Sofía, Zamarreño, Javier, Rodríguez, Sergio, Díaz-Cuervo, Helena, Bueno, Avelino, Sacristán, María P.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/347380
Acceso en línea:http://hdl.handle.net/10261/347380
Access Level:acceso abierto
Palabra clave:Cell biology
Genetics
Molecular biology
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spelling Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stressCañete, Juan A.Andrés, SoniaMuñoz Félix, SofíaZamarreño, JavierRodríguez, SergioDíaz-Cuervo, HelenaBueno, AvelinoSacristán, María P.Cell biologyGeneticsMolecular biologyReactive oxygen species (ROS) are an important source of cellular damage. When ROS intracellular levels increase, oxidative stress takes place affecting DNA stability and metabolic functions. To prevent these effects, stress-activated protein kinases (SAPKs) delay cell cycle progression and induce a transcriptional response that activates antioxidant mechanisms ensuring cell adaptation and survival. Fission yeast Cdc14-like phosphatase Flp1 (also known as Clp1) has a well-established role in cell cycle regulation. Moreover, Flp1 contributes to checkpoint activation during replication stress. Here, we show that Flp1 has a role in fine-tuning the cellular oxidative stress response. Phosphorylation-dependent nucleolar release of Flp1 in response to oxidative stress conditions plays a role in the cellular transcriptional response. Thus, Flp1 ablation increases the transcriptional response to oxidative stress, in both intensity and duration, upregulating both Atf1/Pcr1- and Pap1-dependent stress induced genes. Remarkably, we found that Flp1 interacts with the Atf1/Pcr1 complex with Pcr1 acting as a direct substrate. Our results provide evidence that Flp1 modulates the oxidative stress response by limiting the Atf1/Pcr1-mediated transcription.AB and MS received financial support for this research work through Programa General de Conocimiento (BFU2015-69709-P and PID2019-109616GB-100) and Junta de Castilla y León (SA042P17 and SA103P20) grants from the Spanish Science, Innovation and Universities Ministry and Junta de Castilla y León. JAC was supported by a predoctoral fellowship from the Junta de Castilla y León. AB and MS Institution is supported by the “Programa de Apoyo a Planes Estratégicos de Investigaciόn de Excelencia” cofunded by the Junta de Castilla y Leόn and the European Regional Development Fund (CLC-2017-01).Peer reviewedSpringer NatureMinisterio de Economía y Competitividad (España)Ministerio de Ciencia, Innovación y Universidades (España)Agencia Estatal de Investigación (España)Junta de Castilla y LeónConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2024202420232024info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/347380reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO//BFU2015-69709-Pinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109616GB-I00Cañete, Juan A.; Andrés, Sonia; Muñoz, Sofía; Zamarreño, Javier; Rodríguez, Sergio; Díaz-Cuervo, Helena; Bueno, Avelino; Sacristán, María P.; 2023; Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress [Dataset]; Springer Nature; http://dx.doi.org/10.1038/s41598-023-41869-whttp://dx.doi.org/10.1038/s41598-023-41869-wSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3473802026-05-22T06:33:51Z
dc.title.none.fl_str_mv Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
title Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
spellingShingle Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
Cañete, Juan A.
Cell biology
Genetics
Molecular biology
title_short Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
title_full Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
title_fullStr Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
title_full_unstemmed Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
title_sort Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress
dc.creator.none.fl_str_mv Cañete, Juan A.
Andrés, Sonia
Muñoz Félix, Sofía
Zamarreño, Javier
Rodríguez, Sergio
Díaz-Cuervo, Helena
Bueno, Avelino
Sacristán, María P.
author Cañete, Juan A.
author_facet Cañete, Juan A.
Andrés, Sonia
Muñoz Félix, Sofía
Zamarreño, Javier
Rodríguez, Sergio
Díaz-Cuervo, Helena
Bueno, Avelino
Sacristán, María P.
author_role author
author2 Andrés, Sonia
Muñoz Félix, Sofía
Zamarreño, Javier
Rodríguez, Sergio
Díaz-Cuervo, Helena
Bueno, Avelino
Sacristán, María P.
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Ministerio de Ciencia, Innovación y Universidades (España)
Agencia Estatal de Investigación (España)
Junta de Castilla y León
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Cell biology
Genetics
Molecular biology
topic Cell biology
Genetics
Molecular biology
description Reactive oxygen species (ROS) are an important source of cellular damage. When ROS intracellular levels increase, oxidative stress takes place affecting DNA stability and metabolic functions. To prevent these effects, stress-activated protein kinases (SAPKs) delay cell cycle progression and induce a transcriptional response that activates antioxidant mechanisms ensuring cell adaptation and survival. Fission yeast Cdc14-like phosphatase Flp1 (also known as Clp1) has a well-established role in cell cycle regulation. Moreover, Flp1 contributes to checkpoint activation during replication stress. Here, we show that Flp1 has a role in fine-tuning the cellular oxidative stress response. Phosphorylation-dependent nucleolar release of Flp1 in response to oxidative stress conditions plays a role in the cellular transcriptional response. Thus, Flp1 ablation increases the transcriptional response to oxidative stress, in both intensity and duration, upregulating both Atf1/Pcr1- and Pap1-dependent stress induced genes. Remarkably, we found that Flp1 interacts with the Atf1/Pcr1 complex with Pcr1 acting as a direct substrate. Our results provide evidence that Flp1 modulates the oxidative stress response by limiting the Atf1/Pcr1-mediated transcription.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/347380
url http://hdl.handle.net/10261/347380
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO//BFU2015-69709-P
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-109616GB-I00
Cañete, Juan A.; Andrés, Sonia; Muñoz, Sofía; Zamarreño, Javier; Rodríguez, Sergio; Díaz-Cuervo, Helena; Bueno, Avelino; Sacristán, María P.; 2023; Fission yeast Cdc14-like phosphatase Flp1/Clp1 modulates the transcriptional response to oxidative stress [Dataset]; Springer Nature; http://dx.doi.org/10.1038/s41598-023-41869-w
http://dx.doi.org/10.1038/s41598-023-41869-w
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
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