ArticleThe EMBO journal2006
Antiviral effect of the mammalian translation initiation factor 2alpha kinase GCN2 against RNA viruses.
Article in The EMBO journal, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 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
123 citing papers in PubMed, 198 citations in OpenAlex.
- The oncolytic vesicular stomatitis virus VSV-GP shows profound oncolytic activity in NUT-carcinoma cell lines.Molecular therapy. Oncology · 2026Article
- NUFIP1 at the crossroads of ribophagy and disease: unveiling therapeutic implications.Journal of translational medicine · 2025Review
- ER stress tolerance is regulated by copper-dependent PERK kinase activity.Cell reports · 2025Article
- GCN2 enhances host survival and drives eIF2α phosphorylation during mouse adenovirus type 1 infection.Journal of virology · 2025Article
- The heme-regulated inhibitor kinase Hri1 is activated in response to aminolevulinic acid deficiency in Schizosaccharomyces pombe.PLoS genetics · 2025Article
- Article
- Purification and Analysis of eIF2α Phosphorylation by Stress-Activated Protein Kinase Gcn2 from S. cerevisiae.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway.Cancer gene therapy · 2024Article
- Article
- Cellular Stress Responses against Coronavirus Infection: A Means of the Innate Antiviral Defense.Journal of microbiology and biotechnology · 2024Review
- General control nonderepressible 2 (GCN2) as a therapeutic target in age-related diseases.Frontiers in aging · 2024Review
- Cellular Stress: Modulator of Regulated Cell Death.Biology · 2023Review
- Hepatitis E Virus Protease Inhibits the Activity of Eukaryotic Initiation Factor 2-Alpha Kinase 4 and Promotes Virus Survival.Journal of virology · 2023Article
- Review
- Intestinal GCN2 controlseLife · 2023Article
- Defects in intratumoral arginine metabolism attenuate the replication and therapeutic efficacy of oncolytic myxoma virus.Journal for immunotherapy of cancer · 2023Article
- A little less aggregation a little more replication: Viral manipulation of stress granules.Wiley interdisciplinary reviews. RNA · 2023Review
- Is bRaQCing bad? New roles for ribosome associated quality control factors in stress granule regulation.Biochemical Society transactions · 2022Article
- The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
63 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
8 authors at 4 institutions in 3 countries.
Funding
Abstract
In mammals, four different protein kinases, heme-regulated inhibitor, double-stranded RNA-dependent protein kinase (PKR), general control non-derepressible-2 (GCN2) and PKR-like endoplasmic reticulum kinase, regulate protein synthesis in response to environmental stresses by phosphorylating the alpha-subunit of the initiation factor 2 (eIF2alpha). We now report that mammalian GCN2 is specifically activated in vitro upon binding of two nonadjacent regions of the Sindbis virus (SV) genomic RNA to its histidyl-tRNA synthetase-related domain. Moreover, endogenous GCN2 is activated in cells upon SV infection. Strikingly, fibroblasts derived from GCN2-/- mice possess an increased permissiveness to SV or vesicular stomatitis virus infection. We further show that mice lacking GCN2 are extremely susceptible to intranasal SV infection, demonstrating high virus titers in the brain compared to similarly infected control animals. The overexpression of wild-type GCN2, but not the catalytically inactive GCN2-K618R variant, in NIH 3T3 cells impaired the replication of a number of RNA viruses. We determined that GCN2 inhibits SV replication by blocking early viral translation of genomic SV RNA. These findings point to a hitherto unrecognized role of GCN2 as an early mediator in the cellular response to RNA viruses.
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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.