ArticleCell death discovery2022
Elucidation of an mTORC2-PKC-NRF2 pathway that sustains the ATF4 stress response and identification of Sirt5 as a key ATF4 effector.
Article in Cell death discovery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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Who cites it
13 citing papers in PubMed, 23 citations in OpenAlex.
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Endothelial Ffar4 protects against diabetic kidney disease by potentiating endogenous retinoic acid metabolism.Cellular & molecular biology letters · 2026Article
- Targeting glutamine metabolism as a potential target for cancer treatment.Journal of experimental & clinical cancer research : CR · 2025Review
- Muscle mTOR controls iron homeostasis and ferritinophagy via NRF2, HIFs and AKT/PKB signaling pathways.Cellular and molecular life sciences : CMLS · 2025Article
- Sec10 negatively regulates antiviral immunity by downregulating NRF2-ATF4-RIG-I axis.International journal of biological sciences · 2025Article
- Network-Based Bioinformatics Highlights Broad Importance of Human Milk Hyaluronan.International journal of molecular sciences · 2024Article
- Molecular mechanisms and therapeutic strategies for ferroptosis and cuproptosis in ischemic stroke.Brain, behavior, & immunity - health · 2024Review
- Targeting cellular adaptive responses to glutaminolysis perturbation for cancer therapy.Molecules and cells · 2024Review
- Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer.International journal of molecular sciences · 2024Review
- Aldehyde-mediated inhibition of asparagine biosynthesis has implications for diabetes and alcoholism.Chemical science · 2024Article
- Targeting sirtuins for cancer therapy: epigenetics modifications and beyond.Theranostics · 2024Review
- ReCorDE: a framework for identifying drug classes targeting shared vulnerabilities with applications to synergistic drug discovery.Frontiers in oncology · 2024Article
- Identification of ATF3 as a novel protective signature of quiescent colorectal tumor cells.Cell death & disease · 2023Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Proliferating cancer cells are dependent on glutamine metabolism for survival when challenged with oxidative stresses caused by reactive oxygen species, hypoxia, nutrient deprivation and matrix detachment. ATF4, a key stress responsive transcription factor, is essential for cancer cells to sustain glutamine metabolism when challenged with these various types of stress. While it is well documented how the ATF4 transcript is translated into protein as a stress response, an important question concerns how the ATF4 message levels are sustained to enable cancer cells to survive the challenges of nutrient deprivation and damaging reactive oxygen species. Here, we now identify the pathway in triple negative breast cancer cells that provides a sustained ATF4 response and enables their survival when encountering these challenges. This signaling pathway starts with mTORC2, which upon sensing cellular stresses arising from glutamine deprivation or an acute inhibition of glutamine metabolism, initiates a cascade of events that triggers an increase in ATF4 transcription. Surprisingly, this signaling pathway is not dependent on AKT activation, but rather requires the mTORC2 target, PKC, which activates the transcription factor Nrf2 that then induces ATF4 expression. Additionally, we identify a sirtuin family member, the NAD
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.