2026-08-12T20:56:30Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/72092024-09-27T09:22:04Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Sanchez-Alvarez, Miguel
author
del Pozo, Miguel Angel
author
Bakal, Chris
funder
Biotechnology and Biological Sciences Research Council (Reino Unido)
funder
Cancer Research UK (Reino Unido)
funder
Ministerio de Economía y Competitividad (España)
funder
Worldwide Cancer Research Foundation
funder
Fundación ProCNIC
2019-02-21T11:57:27Z
2019-02-21T11:57:27Z
2017-11-28
Sci Rep. 2017; 7(1):16497
10.1038/s41598-017-16662-1
2045-2322
2045-2322
Scientific reports
29184100
http://hdl.handle.net/20.500.12105/7209
Inositol 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.
eng
AKT-mTOR signaling modulates the dynamics of IRE1 RNAse activity by regulating ER-mitochondria contacts
journal article
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AKT-mTORSignalingModulates_2017.pdf.txt
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