Nrf2 Is a Direct PERK Substrate and Effector of PERK-Dependent Cell Survival

By S. Cullinan, Donna D. Zhang, Mark Hannink, Edward W. Arvisais, R. J. Kaufman, J. Alan Diehl. Molecular and Cellular Biology, 2003

1,236 citations recorded by the source corpus.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/ded287653159bf3291859876765516ac74291d55

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. R. Kaufman
2. C. Hetz
3. D. Ron
4. J. Malhotra
5. Peter Walter
6. Afshin Samali
7. A. Gorman
8. H. Harding

In Molecular Biology

1. R. Kaufman
2. A. Dinkova-Kostova
3. Masayuki Yamamoto
4. C. Hetz
5. D. Ron
6. Liam Baird
7. J. Malhotra
8. Peter Walter

Citations in the corpus

• Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword? (2007, neutral): “NRF2 is a direct PERK substrate and effector of PERK-dependent cell survival (21).”
• Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease (2010, neutral): “PERK-dependent phosphorylation triggers dissociation of Nrf2/Keap1 complexes and allows subsequent Nrf2 nuclear import (Cullinan et al., 2003).”
• Role of nrf2 in oxidative stress and toxicity. (2013, background): “PERK phosphorylates Nrf2 on Thr-80 to activate Nrf2 and induce ARE genes, which increase GSH level, reduce ROS in ER, and promote survival (67, 111) (Figure 3c).”
• Hydrogen peroxide sensing, signaling and regulation of transcription factors (2014, background): “ Phosphorylation catalyzed by protein kinase RNA (PKR)-like ER kinase (PERK), a transmembrane protein kinase that is required for the cellular response to ER stress [223], and that is rapidly activated (15 min) by low extracellular H2O2 levels (15 M) in HeLa cells [224].”
• SCF/β-TrCP Promotes Glycogen Synthase Kinase 3-Dependent Degradation of the Nrf2 Transcription Factor in a Keap1-Independent Manner (2011, background): “Conventional cell signaling studies have suggested that Nrf2 might be regulated by protein phosphorylation (2, 6, 15, 18, 36, 44).”
• Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2 (2004, background): “Stresses on the endoplasmic reticulum were recently reported to activate the Nrf2-Keap1 system through direct phosphorylation of Nrf2 by pancreatic endoplasmic reticulum eukaryotic initiation factor 2 kinase (2).”
• The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. (2013, background): “In addition, PERK kinase has also been shown to phosphorylate Nrf2, but the exact site of phosphorylation is yet to be identified [99].”
• PERK is required at the ER-mitochondrial contact sites to convey apoptosis after ROS-based ER stress (2012, background): “PERK’s function as ER stress sensor and transcriptional regulator of redox homeostasis found in previous reports.(29,30) PERKþ /þ and PERK / cells in fact experience a similar”
• ER stress‐regulated translation increases tolerance to extreme hypoxia and promotes tumor growth (2005, background): “…‘knock-in’ mutation of eIF2a display attenuated induction of ISR genes under hypoxia, and are sensitive to hypoxic stress Although eIF2a phosphorylation is a primary target of activated PERK, it has been suggested that PERK phosphoryla- tion may activate additional targets (Cullinan et al, 2003).”
• Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. (2018, background): “ATF4, a transcription factor, transactivates UPR target genes involved in protein folding, autophagy, redox homeostasis, amino acid metabolism and apoptosis (34, 35).”
• Cellular Stress Responses: Cell Survival and Cell Death (2010, background): “PERK can also directly phosphorylate and activate the transcription factor, NF-E2-related factor-2 (Nrf2), which contributes to cellular redox homeostatis by inducing the expression of anti-oxidant genes [139, 140].”
• Keap1 Is a Redox-Regulated Substrate Adaptor Protein for a Cul3-Dependent Ubiquitin Ligase Complex (2004, neutral): “sensitivity to chemical-induced stresses (4, 10, 13, 18), hyper-”