Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia

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...

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Autores principales:	Blaustein Kappelmacher, Matias, Grande, Alicia Viviana, Risso, Guillermo Javier, Srebrow, Anabella, Colman Lerner, Alejandro Ariel
Publicado:	2013
Materias:	activating transcription factor 6 cell protein initiation factor 2alpha inositol requiring protein 1 PERK protein phosphatidylinositol 3 kinase protein kinase B unclassified drug article cell death cell fate controlled study human human cell hypoxia physiological process protein phosphorylation protein protein interaction protein targeting protein unfolding signal transduction Cell Hypoxia Cell Line Cell Line, Tumor Cell Survival eIF-2 Kinase Eukaryotic Initiation Factor-2 HeLa Cells Humans Proto-Oncogene Proteins c-akt
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n7_p_Blaustein http://hdl.handle.net/20.500.12110/paper_19326203_v8_n7_p_Blaustein
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_19326203_v8_n7_p_Blaustein
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spelling	paper:paper_19326203_v8_n7_p_Blaustein2023-06-08T16:31:17Z Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia Blaustein Kappelmacher, Matias Grande, Alicia Viviana Risso, Guillermo Javier Srebrow, Anabella Colman Lerner, Alejandro Ariel activating transcription factor 6 cell protein initiation factor 2alpha inositol requiring protein 1 PERK protein phosphatidylinositol 3 kinase protein kinase B unclassified drug article cell death cell fate controlled study human human cell hypoxia physiological process protein phosphorylation protein protein interaction protein targeting protein unfolding signal transduction Cell Hypoxia Cell Line Cell Line, Tumor Cell Survival eIF-2 Kinase Eukaryotic Initiation Factor-2 HeLa Cells Humans Proto-Oncogene Proteins c-akt 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. © 2013 Blaustein et al. Fil:Blaustein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Grande, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Risso, G. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Srebrow, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Colman-Lerner, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n7_p_Blaustein http://hdl.handle.net/20.500.12110/paper_19326203_v8_n7_p_Blaustein
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	activating transcription factor 6 cell protein initiation factor 2alpha inositol requiring protein 1 PERK protein phosphatidylinositol 3 kinase protein kinase B unclassified drug article cell death cell fate controlled study human human cell hypoxia physiological process protein phosphorylation protein protein interaction protein targeting protein unfolding signal transduction Cell Hypoxia Cell Line Cell Line, Tumor Cell Survival eIF-2 Kinase Eukaryotic Initiation Factor-2 HeLa Cells Humans Proto-Oncogene Proteins c-akt
spellingShingle	activating transcription factor 6 cell protein initiation factor 2alpha inositol requiring protein 1 PERK protein phosphatidylinositol 3 kinase protein kinase B unclassified drug article cell death cell fate controlled study human human cell hypoxia physiological process protein phosphorylation protein protein interaction protein targeting protein unfolding signal transduction Cell Hypoxia Cell Line Cell Line, Tumor Cell Survival eIF-2 Kinase Eukaryotic Initiation Factor-2 HeLa Cells Humans Proto-Oncogene Proteins c-akt Blaustein Kappelmacher, Matias Grande, Alicia Viviana Risso, Guillermo Javier Srebrow, Anabella Colman Lerner, Alejandro Ariel Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia
topic_facet	activating transcription factor 6 cell protein initiation factor 2alpha inositol requiring protein 1 PERK protein phosphatidylinositol 3 kinase protein kinase B unclassified drug article cell death cell fate controlled study human human cell hypoxia physiological process protein phosphorylation protein protein interaction protein targeting protein unfolding signal transduction Cell Hypoxia Cell Line Cell Line, Tumor Cell Survival eIF-2 Kinase Eukaryotic Initiation Factor-2 HeLa Cells Humans Proto-Oncogene Proteins c-akt
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. © 2013 Blaustein et al.
author	Blaustein Kappelmacher, Matias Grande, Alicia Viviana Risso, Guillermo Javier Srebrow, Anabella Colman Lerner, Alejandro Ariel
author_facet	Blaustein Kappelmacher, Matias Grande, Alicia Viviana Risso, Guillermo Javier Srebrow, Anabella Colman Lerner, Alejandro Ariel
author_sort	Blaustein Kappelmacher, Matias
title	Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia
title_short	Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia
title_full	Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia
title_fullStr	Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia
title_full_unstemmed	Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia
title_sort	modulation of the akt pathway reveals a novel link with perk/eif2α, which is relevant during hypoxia
publishDate	2013
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v8_n7_p_Blaustein http://hdl.handle.net/20.500.12110/paper_19326203_v8_n7_p_Blaustein
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_version_	1768545622408822784

Modulation of the Akt Pathway Reveals a Novel Link with PERK/eIF2α, which Is Relevant during Hypoxia

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