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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/700
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/700 |
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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) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844614497666334720 |
score |
13.070432 |