ArticleThe Biochemical journal2005
GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiation.
Article in The Biochemical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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
93 citing papers in PubMed, 167 citations in OpenAlex.
- Article
- Article
- Propofol attenuates angiogenesis by activating endoplasmic reticulum stress to suppress TFAP2C-driven VEGFA transcription.Apoptosis : an international journal on programmed cell death · 2026Article
- Pre-established ATF4 occupancy and chromatin organization instruct selective transcription activation during integrated stress response.Nature communications · 2025Article
- The integrated stress response suppresses antiviral RNA interference by autophagy-mediated degradation of the RNA-induced silencing complex.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Poxvirus K3 Orthologs Regulate NF-κB-Dependent Inflammatory Responses by Targeting the PKR-eIF2α Axis in Multiple Species.Vaccines · 2025Article
- BRAFbioRxiv : the preprint server for biology · 2024Article
- Multiple mechanisms activate GCN2 eIF2 kinase in response to diverse stress conditions.Nucleic acids research · 2024Article
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Signaling plasticity in the integrated stress response.Frontiers in cell and developmental biology · 2023Review
- Platelet factor 4 (CXCL4/PF4) upregulates matrix metalloproteinase-2 (MMP-2) in gingival fibroblasts.Scientific reports · 2022Article
- Association of selected gene polymorphisms with thermotolerance traits in cattle - A review.Animal bioscience · 2022Article
- Maladaptation after a virus host switch leads to increased activation of the pro-inflammatory NF-κB pathway.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- UV Irradiation of Vaccinia Virus-Infected Cells Impairs Cellular Functions, Introduces Lesions into the Viral Genome, and Uncovers Repair Capabilities for the Viral Replication Machinery.Journal of virology · 2022Article
- Mechanisms tailoring the expression of heat shock proteins to proteostasis challenges.The Journal of biological chemistry · 2022Review
- Analysis of Translational Control in the Integrated Stress Response by Polysome Profiling.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The NF-κB Nucleolar Stress Response Pathway.Biomedicines · 2021Review
- Interplay between stress-related genes may influence Alzheimer's disease development: The results of genetic interaction analyses of human data.Mechanisms of ageing and development · 2021Article
- Translational Control during Cellular Senescence.Molecular and cellular biology · 2021Review
- General Control Non-derepressible 1 (AtGCN1) Is Important for Flowering Time, Plant Growth, Seed Development, and the Transcription/Translation of Specific Genes inFrontiers in plant science · 2021Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
In response to UV irradiation, mammalian cells elicit a gene expression programme designed to repair damage and control cell proliferation and apoptosis. Important members of this stress response include the NF-kappaB (nuclear factor-kappaB) family. However, the mechanisms by which UV irradiation activates NF-kappaB are not well understood. In eukaryotes, a variety of environmental stresses are recognized and remediated by a family of protein kinases that phosphorylate the alpha subunit of eIF2 (eukaryotic initiation factor-2). In the present study we show that NF-kappaB in MEF (murine embryo fibroblast) cells is activated by UV-C and UV-B irradiation through a mechanism requiring eIF2alpha phosphorylation. The primary eIF2alpha kinase in response to UV is GCN2 (general control non-derepressible-2), with PEK/PERK (pancreatic eIF2alpha kinase/RNA-dependent-protein-kinase-like endoplasmic-reticulum kinase) carrying out a secondary function. Our studies indicate that lowered protein synthesis accompanying eIF2alpha phosphorylation, combined with eIF2alpha kinase-independent turnover of IkappaBalpha (inhibitor of kappaBalpha), reduces the levels of IkappaBalpha in response to UV irradiation. Release of NF-kappaB from the inhibitory IkappaBalpha would facilitate NF-kappaB entry into the nucleus and targeted transcriptional control. We also find that loss of GCN2 in MEF cells significantly enhances apoptosis in response to UV exposure similar to that measured in cells deleted for the RelA/p65 subunit of NF-kappaB. These results demonstrate that GCN2 is central to recognition of UV stress, and that eIF2alpha phosphorylation provides resistance to apoptosis in response to this environmental insult.
Indexed as
Identifiers
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.