ReviewAmerican journal of physiology. Endocrinology and metabolism2013
Asparagine synthetase: regulation by cell stress and involvement in tumor biology.
Review in American journal of physiology. Endocrinology and metabolism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 131 papers.
What it found
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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.
A Double Blind, Randomized, Placebo-Controlled Study of CM-AT for the Treatment of Autism in Children With All Levels of Fecal Chymotrypsin (FCT)
An Open-Label Extension Study of CM-AT for the Treatment of Children With Autism With All Levels of Fecal Chymotrypsin
Who cites it
131 citing papers in PubMed, 238 citations in OpenAlex.
- hY3 RNA binds and inhibits ribosomes and modulates the starvation-induced integrated stress response.Nucleic acids research · 2026Article
- Heavy water labeling reveals metabolic flexibility of amino acid and polyamine pathways in mammalian cells.Communications chemistry · 2026Article
- Glutamine metabolic enzymes: to filament or not to filament?Biochemical Society transactions · 2026Review
- PCBP1 regulates alternative splicing of AARS2 in congenital cardiomyopathy.Nature cardiovascular research · 2026Article
- Transcriptional readthrough at Atf4 locus suppresses Rps19bp1 and impairs heart development.Cardiovascular research · 2026Article
- The glutaminase activity of ASNS fuels glutamine metabolism in leukemia.Haematologica · 2026Article
- The Glutamine-α-Ketoglutarate Metabolic Axis Controls Vascular Smooth Muscle Cell Function.Cells · 2026Article
- Article
- Asparaginase enhances CAR-T cell antitumor immunity by asparagine metabolic reprogramming and central memory induction in ALL.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Transcriptional Readthrough atbioRxiv : the preprint server for biology · 2025Article
- PI5P4Kα promotes glucose and iron acquisition to support metabolic fitness in pancreatic cancer.Cell reports · 2025Article
- Manipulating dietary protein and amino acids in the common marmoset Callithrix jacchus impacts circulating metabolites and FGF21 levels.Scientific reports · 2025Article
- Article
- Targeting Asparagine Metabolism in Solid Tumors.Nutrients · 2025Review
- Targeting amino acid in tumor therapy.Frontiers in oncology · 2025Review
- Loss of Elp3 blocks intestinal tuft cell differentiation via an mTORC1-Atf4 axis.The EMBO journal · 2024Article
- Differential effect of asparagine and glutamine removal on three adenocarcinoma cell lines.Heliyon · 2024Article
- ATF4 inhibits tumor development and mediates p-GCN2/ASNS upregulation in colon cancer.Scientific reports · 2024Article
- Crosstalk between autophagy and metabolism: implications for cell survival in acute myeloid leukemia.Cell death discovery · 2024Review
- Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.Nature cancer · 2024Article
71 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
3 authors at 1 institution in 1 country.
Funding
Abstract
Asparagine synthetase (ASNS) catalyzes the conversion of aspartate and glutamine to asparagine and glutamate in an ATP-dependent reaction. The enzyme is ubiquitous in its organ distribution in mammals, but basal expression is relatively low in tissues other than the exocrine pancreas. Human ASNS activity is highly regulated in response to cell stress, primarily by increased transcription from a single gene located on chromosome 7. Among the genomic elements that control ASNS transcription is the C/EBP-ATF response element (CARE) within the promoter. Protein limitation or an imbalanced dietary amino acid composition activate the ASNS gene through the amino acid response (AAR), a process that is replicated in cell culture through limitation for any single essential amino acid. Endoplasmic reticulum stress also increases ASNS transcription through the PERK-eIF2-ATF4 arm of the unfolded protein response (UPR). Both the AAR and UPR lead to increased synthesis of ATF4, which binds to the CARE and induces ASNS transcription. Elevated expression of ASNS protein is associated with resistance to asparaginase therapy in childhood acute lymphoblastic leukemia and may be a predictive factor in drug sensitivity for certain solid tumors as well. Activation of the GCN2-eIF2-ATF4 signaling pathway, leading to increased ASNS expression appears to be a component of solid tumor adaptation to nutrient deprivation and/or hypoxia. Identifying the roles of ASNS in fetal development, tissue differentiation, and tumor growth may reveal that ASNS function extends beyond asparagine biosynthesis.
Indexed as
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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.