Genome-Wide CRISPR Screen Reveals Autophagy Disruption as the Convergence Mechanism That Regulates the NRF2 Transcription Factor.
CRISPR
KEAP1
NFE2L2
NRF2
autophagy
gene reporters
genomics
molecular biology
oxidative stress
signal transduction
Journal
Molecular and cellular biology
ISSN: 1098-5549
Titre abrégé: Mol Cell Biol
Pays: United States
ID NLM: 8109087
Informations de publication
Date de publication:
01 07 2019
01 07 2019
Historique:
received:
23
01
2019
accepted:
14
04
2019
pubmed:
24
4
2019
medline:
6
2
2020
entrez:
24
4
2019
Statut:
epublish
Résumé
The nuclear factor (erythroid 2)-like 2 (NRF2 or NFE2L2) transcription factor regulates the expression of many genes that are critical in maintaining cellular homeostasis. Its deregulation has been implicated in many diseases, including cancer and metabolic and neurodegenerative diseases. While several mechanisms by which NRF2 can be activated have gradually been identified over time, a more complete regulatory network of NRF2 is still lacking. Here we show through a genome-wide clustered regularly interspaced short palindromic repeat (CRISPR) screen that a total of 273 genes, when knocked out, will lead to sustained NRF2 activation. Pathway analysis revealed a significant overrepresentation of genes (18 of the 273 genes) involved in autophagy. Molecular validation of a subset of the enriched genes identified 8 high-confidence genes that negatively regulate NRF2 activity irrespective of cell type:
Identifiants
pubmed: 31010806
pii: MCB.00037-19
doi: 10.1128/MCB.00037-19
pmc: PMC6580702
pii:
doi:
Substances chimiques
NF-E2-Related Factor 2
0
NFE2L2 protein, human
0
RNA, Guide
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES006694
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA226920
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109555
Pays : United States
Organisme : NIEHS NIH HHS
ID : R21 ES027920
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
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