Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia

Autores
Blaustein Kappelmacher, Matias; Pérez-Munizaga, Daniela; Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia Viviana; Risso, Guillermo; Srebrow, Anabella; Alfaro, Jennifer; Colman Lerner, Alejandro Ariel
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug Akt-IV strongly and persistently activated all three branches of the UPR. We present evidence that activation of PERK/eIF2α requires Akt and that PERK is a direct Akt target. Chemical activation of this novel Akt/PERK pathway by Akt-IV leads to cell death, which was largely dependent on the presence of PERK and IRE1. Finally, we show that hypoxia-induced activation of eIF2α requires Akt, providing a physiologically relevant condition for the interaction between Akt and the PERK branch of the UPR. These data suggest the UPR and the Akt pathway signal to one another as a means of controlling cell fate.
Fil: Blaustein Kappelmacher, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Pérez-Munizaga, Daniela. Fundación Ciencia y Vida; Chile;
Fil: Sánchez, Manuel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Urrutia, Carolina. Fundación Ciencia y Vida; Chile;
Fil: Grande, Alicia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Risso, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Srebrow, Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Alfaro, Jennifer. Fundación Ciencia y Vida; Chile;
Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Materia
Akt
UPR
PERK
Hypoxia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/700

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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxiaBlaustein Kappelmacher, MatiasPérez-Munizaga, DanielaSánchez, Manuel AlejandroUrrutia, CarolinaGrande, Alicia VivianaRisso, GuillermoSrebrow, AnabellaAlfaro, JenniferColman Lerner, Alejandro ArielAktUPRPERKHypoxiahttps://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug Akt-IV strongly and persistently activated all three branches of the UPR. We present evidence that activation of PERK/eIF2α requires Akt and that PERK is a direct Akt target. Chemical activation of this novel Akt/PERK pathway by Akt-IV leads to cell death, which was largely dependent on the presence of PERK and IRE1. Finally, we show that hypoxia-induced activation of eIF2α requires Akt, providing a physiologically relevant condition for the interaction between Akt and the PERK branch of the UPR. These data suggest the UPR and the Akt pathway signal to one another as a means of controlling cell fate.Fil: Blaustein Kappelmacher, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;Fil: Pérez-Munizaga, Daniela. Fundación Ciencia y Vida; Chile;Fil: Sánchez, Manuel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;Fil: Urrutia, Carolina. Fundación Ciencia y Vida; Chile;Fil: Grande, Alicia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;Fil: Risso, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;Fil: Srebrow, Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;Fil: Alfaro, Jennifer. Fundación Ciencia y Vida; Chile;Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;Public Library Science2013-07-29info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/700Blaustein Kappelmacher, Matias; Pérez-Munizaga, Daniela; Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia Viviana; et al.;Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia; Public Library Science; Plos One; 8; 7; 7-2013; e0696681932-6203enginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0069668info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:45:46Zoai:ri.conicet.gov.ar:11336/700instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:45:46.31CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
title Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
spellingShingle Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
Blaustein Kappelmacher, Matias
Akt
UPR
PERK
Hypoxia
title_short Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
title_full Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
title_fullStr Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
title_full_unstemmed Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
title_sort Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia
dc.creator.none.fl_str_mv Blaustein Kappelmacher, Matias
Pérez-Munizaga, Daniela
Sánchez, Manuel Alejandro
Urrutia, Carolina
Grande, Alicia Viviana
Risso, Guillermo
Srebrow, Anabella
Alfaro, Jennifer
Colman Lerner, Alejandro Ariel
author Blaustein Kappelmacher, Matias
author_facet Blaustein Kappelmacher, Matias
Pérez-Munizaga, Daniela
Sánchez, Manuel Alejandro
Urrutia, Carolina
Grande, Alicia Viviana
Risso, Guillermo
Srebrow, Anabella
Alfaro, Jennifer
Colman Lerner, Alejandro Ariel
author_role author
author2 Pérez-Munizaga, Daniela
Sánchez, Manuel Alejandro
Urrutia, Carolina
Grande, Alicia Viviana
Risso, Guillermo
Srebrow, Anabella
Alfaro, Jennifer
Colman Lerner, Alejandro Ariel
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Akt
UPR
PERK
Hypoxia
topic Akt
UPR
PERK
Hypoxia
purl_subject.fl_str_mv https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
dc.description.none.fl_txt_mv The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug Akt-IV strongly and persistently activated all three branches of the UPR. We present evidence that activation of PERK/eIF2α requires Akt and that PERK is a direct Akt target. Chemical activation of this novel Akt/PERK pathway by Akt-IV leads to cell death, which was largely dependent on the presence of PERK and IRE1. Finally, we show that hypoxia-induced activation of eIF2α requires Akt, providing a physiologically relevant condition for the interaction between Akt and the PERK branch of the UPR. These data suggest the UPR and the Akt pathway signal to one another as a means of controlling cell fate.
Fil: Blaustein Kappelmacher, Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Pérez-Munizaga, Daniela. Fundación Ciencia y Vida; Chile;
Fil: Sánchez, Manuel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Urrutia, Carolina. Fundación Ciencia y Vida; Chile;
Fil: Grande, Alicia Viviana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Risso, Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Srebrow, Anabella. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
Fil: Alfaro, Jennifer. Fundación Ciencia y Vida; Chile;
Fil: Colman Lerner, Alejandro Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentina;
description The unfolded protein response (UPR) and the Akt signaling pathway share several regulatory functions and have the capacity to determine cell outcome under specific conditions. However, both pathways have largely been studied independently. Here, we asked whether the Akt pathway regulates the UPR. To this end, we used a series of chemical compounds that modulate PI3K/Akt pathway and monitored the activity of the three UPR branches: PERK, IRE1 and ATF6. The antiproliferative and antiviral drug Akt-IV strongly and persistently activated all three branches of the UPR. We present evidence that activation of PERK/eIF2α requires Akt and that PERK is a direct Akt target. Chemical activation of this novel Akt/PERK pathway by Akt-IV leads to cell death, which was largely dependent on the presence of PERK and IRE1. Finally, we show that hypoxia-induced activation of eIF2α requires Akt, providing a physiologically relevant condition for the interaction between Akt and the PERK branch of the UPR. These data suggest the UPR and the Akt pathway signal to one another as a means of controlling cell fate.
publishDate 2013
dc.date.none.fl_str_mv 2013-07-29
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/700
Blaustein Kappelmacher, Matias; Pérez-Munizaga, Daniela; Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia Viviana; et al.;Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia; Public Library Science; Plos One; 8; 7; 7-2013; e069668
1932-6203
url http://hdl.handle.net/11336/700
identifier_str_mv Blaustein Kappelmacher, Matias; Pérez-Munizaga, Daniela; Sánchez, Manuel Alejandro; Urrutia, Carolina; Grande, Alicia Viviana; et al.;Modulation of the Akt pathway reveals a novel link with PERK/eIF2alpha, which is relevant during hypoxia; Public Library Science; Plos One; 8; 7; 7-2013; e069668
1932-6203
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pone.0069668
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library Science
publisher.none.fl_str_mv Public Library Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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