ArticleThe Journal of biological chemistry2009
Elevated ATF4 expression, in the absence of other signals, is sufficient for transcriptional induction via CCAAT enhancer-binding protein-activating transcription factor response elements.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 60 citations in OpenAlex.
- Regulation of Translation of ATF4 mRNA: A Focus on Translation Initiation Factors and RNA-Binding Proteins.Cells · 2026Review
- Anoikis resistance and cancer.BMC cancer · 2025Review
- CRISPuRe-seq: pooled screening of barcoded ribonucleoprotein reporters reveals regulation of RNA polymerase III transcription by the integrated stress response via mTOR.Nucleic acids research · 2025Article
- Genome-wide census of ATF4 binding sites and functional profiling of trait-associated genetic variants overlapping ATF4 binding motifs.PLoS genetics · 2023Article
- The Origins, Evolution, and Future of Dietary Methionine Restriction.Annual review of nutrition · 2022Review
- Review
- Brown adipocyte ATF4 activation improves thermoregulation and systemic metabolism.Cell reports · 2021Article
- HepaticNutrients · 2021Article
- DENR promotes translation reinitiation via ribosome recycling to drive expression of oncogenes including ATF4.Nature communications · 2020Article
- A human-specific VNTR in the TRIB3 promoter causes gene expression variation between individuals.PLoS genetics · 2020Article
- The gene for the lysosomal protein LAMP3 is a direct target of the transcription factor ATF4.The Journal of biological chemistry · 2020Article
- Nutritional Regulation of Gene Expression: Carbohydrate-, Fat- and Amino Acid-Dependent Modulation of Transcriptional Activity.International journal of molecular sciences · 2019Review
- The Beta-adrenergic agonist, Ractopamine, increases skeletal muscle expression of Asparagine Synthetase as part of an integrated stress response gene program.Scientific reports · 2018Article
- Sensing and signaling mechanisms linking dietary methionine restriction to the behavioral and physiological components of the response.Frontiers in neuroendocrinology · 2018Review
- GCN2- and eIF2α-phosphorylation-independent, but ATF4-dependent, induction of CARE-containing genes in methionine-deficient cells.Amino acids · 2016Article
- The C/ebp-Atf response element (CARE) location reveals two distinct Atf4-dependent, elongation-mediated mechanisms for transcriptional induction of aminoacyl-tRNA synthetase genes in response to amino acid limitation.Nucleic acids research · 2016Article
- Emerging tale of UPR and cancer: an essentiality for malignancy.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Endoplasmic Reticulum Stress Signaling in Plant Immunity--At the Crossroad of Life and Death.International journal of molecular sciences · 2015Review
- Cell intrinsic and extrinsic activators of the unfolded protein response in cancer: Mechanisms and targets for therapy.Seminars in cancer biology · 2015Review
- MAPK signaling triggers transcriptional induction of cFOS during amino acid limitation of HepG2 cells.Biochimica et biophysica acta · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Protein limitation in vivo or amino acid deprivation of cells in culture causes a signal transduction cascade consisting of activation of the kinase GCN2 (general control nonderepressible 2), phosphorylation of eukaryotic initiation factor 2, and increased synthesis of activating transcription factor (ATF) 4 by a translational control mechanism. In a self-limiting transcriptional program, ATF4 transiently activates a wide range of downstream target genes involved in transport, cellular metabolism, and other cell functions. Simultaneous activation of other signal transduction pathways by amino acid deprivation led to the question of whether or not the increased abundance of ATF4 alone was sufficient to trigger the transcriptional control mechanisms. Using 293 cells that ectopically express ATF4 in a tetracycline-inducible manner showed that ATF4 target genes were activated in the absence of amino acid deprivation. Ectopic expression of ATF4 alone resulted in effective recruitment of the general transcription machinery, but some reduction in histone modification was observed. These data document that ATF4 alone is sufficient to trigger the amino acid-responsive transcriptional control program. However, the absolute amount of ectopic ATF4 required to achieve the same degree of transcriptional activation observed after amino acid limitation was greater, suggesting that other factors may serve to enhance ATF4 function.
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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.