PMID- 32121537
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 12
IP  - 3
DP  - 2020 Mar 1
TI  - ATF4-Dependent NRF2 Transcriptional Regulation Promotes Antioxidant Protection 
      during Endoplasmic Reticulum Stress.
LID - 10.3390/cancers12030569 [doi]
LID - 569
AB  - Endoplasmic reticulum (ER) stress generates reactive oxygen species (ROS) that 
      induce apoptosis if left unabated. To limit oxidative insults, the ER stress 
      PKR-like endoplasmic reticulum Kinase (PERK) has been reported to phosphorylate 
      and activate nuclear factor erythroid 2-related factor 2 (NRF2). Here, we uncover 
      an alternative mechanism for PERK-mediated NRF2 regulation in human cells that 
      does not require direct phosphorylation. We show that the activation of the PERK 
      pathway rapidly stimulates the expression of NRF2 through activating 
      transcription factor 4 (ATF4). In addition, NRF2 activation is late and largely 
      driven by reactive oxygen species (ROS) generated during late protein synthesis 
      recovery, contributing to protecting against cell death. Thus, PERK-mediated NRF2 
      activation encompasses a PERK-ATF4-dependent control of NRF2 expression that 
      contributes to the NRF2 protective response engaged during ER stress-induced ROS 
      production.
FAU - Sarcinelli, Carmen
AU  - Sarcinelli C
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Dragic, Helena
AU  - Dragic H
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Piecyk, Marie
AU  - Piecyk M
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Barbet, Virginie
AU  - Barbet V
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Duret, Cedric
AU  - Duret C
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Barthelaix, Audrey
AU  - Barthelaix A
AD  - Institute for Regenerative Medicine and Biotherapy, Montpellier, 34295, France.
FAU - Ferraro-Peyret, Carole
AU  - Ferraro-Peyret C
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
AD  - Hospices Civils de Lyon, Centre de pathologie Est, Bron69500, France.
FAU - Fauvre, Joelle
AU  - Fauvre J
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Renno, Toufic
AU  - Renno T
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Chaveroux, Cedric
AU  - Chaveroux C
AUID- ORCID: 0000-0002-4116-3354
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
FAU - Manie, Serge N
AU  - Manie SN
AD  - Centre de Recherche en Cancerologie de Lyon, INSERM U1052, CNRS 5286, Centre Leon 
      Berard, Univ Lyon, Universite Claude Bernard Lyon 1, Lyon, 69373, France.
AD  - Inserm U1242, Universite de Rennes, Centre de Lutte Contre le Cancer Eugene 
      Marquis, Rennes 35042, France.
LA  - eng
GR  - INCA_7981/Institut National Du Cancer/
GR  - R16173CC/Fondation ARC pour la Recherche sur le Cancer/
GR  - R17167CC, R18159CC/Ligue Contre le Cancer/
PT  - Journal Article
DEP - 20200301
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC7139862
OTO - NOTNLM
OT  - ATF4
OT  - ER stress
OT  - NRF2
OT  - PERK
OT  - ROS
COIS- The authors declare no conflict of interest.
EDAT- 2020/03/04 06:00
MHDA- 2020/03/04 06:01
PMCR- 2020/03/01
CRDT- 2020/03/04 06:00
PHST- 2020/02/04 00:00 [received]
PHST- 2020/02/24 00:00 [revised]
PHST- 2020/02/27 00:00 [accepted]
PHST- 2020/03/04 06:00 [entrez]
PHST- 2020/03/04 06:00 [pubmed]
PHST- 2020/03/04 06:01 [medline]
PHST- 2020/03/01 00:00 [pmc-release]
AID - cancers12030569 [pii]
AID - cancers-12-00569 [pii]
AID - 10.3390/cancers12030569 [doi]
PST - epublish
SO  - Cancers (Basel). 2020 Mar 1;12(3):569. doi: 10.3390/cancers12030569.