ArticleNeuron2019
The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.
Article in Neuron, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- A Systematic Review of Lymphangioleiomyomatosis on Diagnosis and Molecular Mechanism.BioMed research international · 2021Pooled it
- From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.International journal of molecular sciences · 2026Review
- ATF4: Orchestrating Cellular Stress Adaptation, Metabolism, and Immune Regulation in Health and Disease.International journal of molecular sciences · 2026Review
- Article
- Circadian clock control of ribosome composition promotes rhythmic translation and termination fidelity.Cell reports · 2025Article
- Rhythmic Dynamics of Stress Granules inInternational journal of molecular sciences · 2025Article
- Circadian rhythms in metabolism and mental health: a reciprocal regulatory network with implications for metabolic and neuropsychiatric disorders.Current opinion in physiology · 2025Review
- Emerging roles for integrated stress response signaling in homeostasis.The FEBS journal · 2025Review
- Review
- Amino Acid-Sensing Neurons in the Anterior Piriform Cortex Control Brown Adipose Tissue Thermogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulatory links between the circadian clock and stress-induced biomolecular condensates.Npj biological timing and sleep · 2025Review
- An ISR-independent role of GCN2 prevents excessive ribosome biogenesis and mRNA translation.Life science alliance · 2025Article
- Circadian Control of Protein Synthesis.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Circadian clock control of interactions between eIF2α kinase CPC-3 and GCN1 with ribosomes regulates rhythmic translation initiation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- The Deubiquitinase USP2 Modulates Photic Entrainment of the Circadian Clock at the Level of the Suprachiasmatic Nucleus.Journal of neurochemistry · 2025Article
- Emerging Molecular-Genetic Families in Dystonia: Endosome-Autophagosome-Lysosome and Integrated Stress Response Pathways.Movement disorders : official journal of the Movement Disorder Society · 2025Review
- Chemogenetic neuronal silencing decouples c-Jun activation from cell death in the temporal cortex.The European journal of neuroscience · 2024Article
- GCN2 drives diurnal patterns in the hepatic integrated stress response and maintains circadian rhythms in whole body metabolism during amino acid insufficiency.American journal of physiology. Endocrinology and metabolism · 2024Article
- Sleep-wake behavior and responses to sleep deprivation and immune challenge of protein kinase RNA-activated knockout mice.Brain, behavior, and immunity · 2024Article
- The integrated stress response in brain diseases: A double-edged sword for proteostasis and synapses.Current opinion in neurobiology · 2024Review
Corrections and comments
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Authors and funding
15 authors at 8 institutions in 2 countries.
Funding
Abstract
The integrated stress response (ISR) is activated in response to diverse stress stimuli to maintain homeostasis in neurons. Central to this process is the phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α). Here, we report a critical role for ISR in regulating the mammalian circadian clock. The eIF2α kinase GCN2 rhythmically phosphorylates eIF2α in the suprachiasmatic circadian clock. Increased eIF2α phosphorylation shortens the circadian period in both fibroblasts and mice, whereas reduced eIF2α phosphorylation lengthens the circadian period and impairs circadian rhythmicity in animals. Mechanistically, phosphorylation of eIF2α promotes mRNA translation of Atf4. ATF4 binding motifs are identified in multiple clock genes, including Per2, Per3, Cry1, Cry2, and Clock. ATF4 binds to the TTGCAGCA motif in the Per2 promoter and activates its transcription. Together, these results demonstrate a significant role for ISR in circadian physiology and provide a potential link between dysregulated ISR and circadian dysfunction in brain diseases.
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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.