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dc.contributor.authorSanchez-Alvarez, Miguel 
dc.contributor.authordel Pozo, Miguel Angel 
dc.contributor.authorBakal, Chris
dc.identifier.citationSci Rep. 2017; 7(1):16497es_ES
dc.descriptionThis work was supported by a project grant from the Biotechnology and Biological Sciences Research Council (BB/J017183/1) and a Cancer Research UK Programme Foundation Award (C37275/1A20146) to C.Bakal; and a Spanish Ministry of Economy and Competitiveness (MINECO) project grant (SAF2014-51876-R) and a Worldwide Cancer Research Foundation project grant (15-0404) to MA del Pozo. M Sanchez-Alvarez is a CNIC IPP fellow (COFUND programme 2014). The CNIC is supported by the Spanish Ministry of Economy and Competitiveness (MINECO) and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (MINECO award SEV-2015-0505).es_ES
dc.description.abstractInositol Requiring Enzyme-1 (IRE1) is the most conserved transducer of the Unfolded Protein Response (UPR), a surveillance mechanism that ensures homeostasis of the endoplasmic reticulum (ER) in eukaryotes. IRE1 activation orchestrates adaptive responses, including lipid anabolism, metabolic reprogramming, increases in protein folding competency, and ER expansion/remodeling. However, we still know surprisingly little regarding the principles by which this ER transducer is deactivated upon ER stress clearance. Here we show that Protein Kinase B-mechanistic Target of Rapamycin (PKB/AKT-mTOR) signaling controls the dynamics of IRE1 deactivation by regulating ER-mitochondria physical contacts and the autophosphorylation state of IRE1. AKT-mTOR-mediated attenuation of IRE1 activity is important for ER remodelling dynamics and cell survival in the face of recursive, transient ER stress. Our observations suggest that IRE1 attenuation is an integral component of anabolic programmes regulated by AKT-mTOR. We suggest that AKT-mTOR activity is part of a 'timing mechanism' to deactivate IRE1 immediately following engagement of the UPR, in order to limit prolonged IRE1 RNAse activity that could lead to damaging inflammation or apoptosis.es_ES
dc.publisherNature Publishing Group es_ES
dc.titleAKT-mTOR signaling modulates the dynamics of IRE1 RNAse activity by regulating ER-mitochondria contactses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderBiotechnology and Biological Sciences Research Council (Reino Unido)
dc.contributor.funderCancer Research UK (Reino Unido)
dc.contributor.funderMinisterio de Economía y Competitividad (España)
dc.contributor.funderWorldwide Cancer Research Foundation
dc.contributor.funderFundación ProCNIC
dc.identifier.journalScientific reportses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Señalización por Integrinases_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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