ArticleAging2013
eIF2α phosphorylation bypasses premature senescence caused by oxidative stress and pro-oxidant antitumor therapies.
Article in Aging, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Mitochondria-Associated Membranes in Aging and Senescence.Aging and disease · 2024Review
- Pifithrin-µ Induces Stress Granule Formation, Regulates Cell Survival, and Rewires Cellular Signaling.Cells · 2024Article
- Integrated Stress Response (ISR) Pathway: Unraveling Its Role in Cellular Senescence.International journal of molecular sciences · 2023Review
- Regulation and function of elF2B in neurological and metabolic disorders.Bioscience reports · 2022Review
- Lysosomal TRPML1 regulates mitochondrial function in hepatocellular carcinoma cells.Journal of cell science · 2022Article
- Phosphorylation of eIF2α Promotes Schwann Cell Differentiation and Myelination in CMT1B Mice with Activated UPR.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Roles of the Translation Initiation Factor eIF2α Phosphorylation in Cell Structure and Function.Cell structure and function · 2020Article
- RITA requires eIF2α-dependent modulation of mRNA translation for its anti-cancer activity.Cell death & disease · 2019Article
- Article
- Downregulation of PERK activity and eIF2α serine 51 phosphorylation by mTOR complex 1 elicits pro-oxidant and pro-death effects in tuberous sclerosis-deficient cells.Cell death & disease · 2018Article
- Endoplasmic Reticulum Unfolded Protein Response, Aging and Exercise: An Update.Frontiers in physiology · 2018Review
- Increased phosphorylation of eIF2α in chronic myeloid leukemia cells stimulates secretion of matrix modifying enzymes.Oncotarget · 2016Article
- The eIF2α serine 51 phosphorylation-ATF4 arm promotes HIPPO signaling and cell death under oxidative stress.Oncotarget · 2016Article
- mTORC1 and CK2 coordinate ternary and eIF4F complex assembly.Nature communications · 2016Article
- The protein activator of protein kinase R, PACT/RAX, negatively regulates protein kinase R during mouse anterior pituitary development.The FEBS journal · 2015Article
- Cell intrinsic and extrinsic activators of the unfolded protein response in cancer: Mechanisms and targets for therapy.Seminars in cancer biology · 2015Review
- Stat1 stimulates cap-independent mRNA translation to inhibit cell proliferation and promote survival in response to antitumor drugs.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Phosphorylation of the translation initiation factor eIF2α at serine 51 determines the cell fate decisions of Akt in response to oxidative stress.Cell death & disease · 2015Article
- Evidence for eIF2α phosphorylation-independent effects of GSK2656157, a novel catalytic inhibitor of PERK with clinical implications.Cell cycle (Georgetown, Tex.) · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Eukaryotic cells respond to various forms of stress by blocking mRNA translation initiation via the phosphorylation of the alpha (α) subunit of eIF2 at serine 51 (S51) (eIFαP). An important role of eIF2αP is the regulation of redox homeostasis and adaptation of cells to oxidative stress. Herein, we demonstrate that eIF2αP guards cells from intracellular reactive oxygen species (ROS) via the inhibition of senescence. Specifically, genetic inactivation of either eIF2αP or eIF2α kinase PERK in primary mouse or human fibroblasts leads to proliferative defects associated with increased DNA damage, G2/M accumulation and induction of premature senescence. Impaired proliferation of either PERK or eIF2αP-deficient primary cells is caused by increased ROS and restored by anti-oxidant treatment. Contrary to primary cells, impaired eIF2αP in immortalized mouse fibroblasts or human tumor cells provides tolerance to elevated intracellular ROS levels. However, eIF2αP-deficient human tumor cells are highly susceptible to extrinsic ROS generated by the pro-oxidant drug doxorubicin by undergoing premature senescence. Our work demonstrates that eIF2αP determines cell destiny through its capacity to control senescence in response to oxidative stress. Also, inhibition of eIF2αP may be a suitable means to increase the anti-tumor effects of pro-oxidant drugs through the induction of senescence.
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What OpenQuestion holds
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.