ArticleOncotarget2016
The eIF2α serine 51 phosphorylation-ATF4 arm promotes HIPPO signaling and cell death under oxidative stress.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
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- NDR2 Kinase Regulates Microglial Metabolic Adaptation and Inflammatory Response: Critical Role in Glucose-Dependent Functional Plasticity.International journal of molecular sciences · 2025Article
- Mitochondria-Nuclear Crosstalk: Orchestrating mtDNA Maintenance.Environmental and molecular mutagenesis · 2025Review
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- The NDR family of kinases: essential regulators of aging.Frontiers in molecular neuroscience · 2024Review
- Hippo Signaling Pathway in Colorectal Cancer: Modulation by Various Signals and Therapeutic Potential.Analytical cellular pathology (Amsterdam) · 2024Review
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- A stay of execution: ATF4 regulation and potential outcomes for the integrated stress response.Frontiers in molecular neuroscience · 2023Review
- SCF-SKP2 E3 ubiquitin ligase links mTORC1/ER stress/ISR with YAP activation in murine renal cystogenesis.The Journal of clinical investigation · 2022Article
- Review
- Oxidative stress-CBP axis modulates MOB1 acetylation and activates the Hippo signaling pathway.Nucleic acids research · 2022Article
- E3 ubiquitin ligase Nedd4-2 exerts neuroprotective effects during endoplasmic reticulum stress.Journal of neurochemistry · 2022Article
- The emerging role of WWP1 in cancer development and progression.Cell death discovery · 2021Review
- Ubiquitin-related processes and innate immunity in C. elegans.Cellular and molecular life sciences : CMLS · 2021Review
- Senescence of Alveolar Type 2 Cells Drives Progressive Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2021Article
- The regulatory networks of the Hippo signaling pathway in cancer development.Journal of Cancer · 2021Review
- It takes two to tango: coupling of Hippo pathway and redox signaling in biological process.Cell cycle (Georgetown, Tex.) · 2020Review
- ACADL plays a tumor-suppressor role by targeting Hippo/YAP signaling in hepatocellular carcinoma.NPJ precision oncology · 2020Article
- Functional validation of ATF4 and GADD34 in Neuro2a cells by CRISPR/Cas9-mediated genome editing.Molecular and cellular biochemistry · 2018Article
- YAP/TAZ-mediated activation of serine metabolism and methylation regulation is critical for LKB1-deficient breast cancer progression.Bioscience reports · 2017Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HIPPO pathway is an evolutionary conserved regulator of organ size that controls both cell proliferation and death. This pathway has an important role in mediating cell death in response to oxidative stress through the inactivation of Yes-associated protein (YAP) and inhibition of anti-oxidant gene expression. Cells exposed to oxidative stress induce the phosphorylation of the alpha (α) subunit of the translation initiation factor eIF2 at serine 51 (eIF2αP), a modification that leads to the general inhibition of mRNA translation initiation. Under these conditions, increased eIF2αP facilitates the mRNA translation of activating transcription factor 4 (ATF4), which mediates either cell survival and adaptation or cell death under conditions of severe stress. Herein, we demonstrate a functional connection between the HIPPO and eIF2αP-ATF4 pathways under oxidative stress. We demonstrate that ATF4 promotes the stabilization of the large tumor suppressor 1 (LATS1), which inactivates YAP by phosphorylation. ATF4 inhibits the expression of NEDD4.2 and WWP1 mRNAs under pro-oxidant conditions, which encode ubiquitin ligases mediating the proteasomal degradation of LATS1. Increased LATS1 stability is required for the induction of cell death under oxidative stress. Our data reveal a previously unidentified ATF4-dependent pathway in the induction of cell death under oxidative stress via the activation of LATS1 and HIPPO pathway.
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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.