ArticleThe Journal of biological chemistry2012
Functional RNA interference (RNAi) screen identifies system A neutral amino acid transporter 2 (SNAT2) as a mediator of arsenic-induced endoplasmic reticulum stress.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 34 citations in OpenAlex.
- Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway.Cancer gene therapy · 2024Article
- Endoplasmic reticulum stress induces hepatic steatosis through interaction between PPARα and FoxO6 in vivo and in vitro.Journal of molecular medicine (Berlin, Germany) · 2024Article
- Senataxin deficiency disrupts proteostasis through nucleolar ncRNA-driven protein aggregation.The Journal of cell biology · 2024Article
- Intercellular Transmission of Hepatic ER Stress in Obesity Disrupts Systemic Metabolism.Cell metabolism · 2021Article
- Interaction between CHOP and FoxO6 promotes hepatic lipid accumulation.Liver international : official journal of the International Association for the Study of the Liver · 2020Article
- MicroRNA-124 Reduces Arsenic-induced Endoplasmic Reticulum Stress and Neurotoxicity and is Linked with Neurodevelopment in Children.Scientific reports · 2020Article
- Genome-wide CRISPR screen identifies suppressors of endoplasmic reticulum stress-induced apoptosis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- CDK7 is a component of the integrated stress response regulating SNAT2 (SLC38A2)/System A adaptation in response to cellular amino acid deprivation.Biochimica et biophysica acta. Molecular cell research · 2019Article
- Inhibition of protein disulfide isomerase in glioblastoma causes marked downregulation of DNA repair and DNA damage response genes.Theranostics · 2019Article
- Systematic analyses of glutamine and glutamate metabolisms across different cancer types.Chinese journal of cancer · 2017Article
- shRNA target prediction informed by comprehensive enquiry (SPICE): a supporting system for high-throughput screening of shRNA library.EURASIP journal on bioinformatics & systems biology · 2016Article
- Biological and environmental hazards associated with exposure to chemical warfare agents: arsenicals.Annals of the New York Academy of Sciences · 2016Review
- A Novel Luciferase Assay For Sensitively Monitoring Myocilin Variants in Cell Culture.Investigative ophthalmology & visual science · 2016Article
- Tunicamycin-induced unfolded protein response in the developing mouse brain.Toxicology and applied pharmacology · 2015Article
- The SLC38 family of sodium-amino acid co-transporters.Pflugers Archiv : European journal of physiology · 2014Review
- Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption.Toxicology and applied pharmacology · 2013Article
- Association between arsenic suppression of adipogenesis and induction of CHOP10 via the endoplasmic reticulum stress response.Environmental health perspectives · 2013Article
- Genetic susceptible locus in NOTCH2 interacts with arsenic in drinking water on risk of type 2 diabetes.PloS one · 2013Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Exposure to the toxic metalloid arsenic is associated with diabetes and cancer and causes proteotoxicity and endoplasmic reticulum (ER) stress at the cellular level. Adaptive responses to ER stress are implicated in cancer and diabetes; thus, understanding mechanisms of arsenic-induced ER stress may offer insights into pathogenesis. Here, we identify genes required for arsenite-induced ER stress response in a genome-wide RNAi screen. Using an shRNA library targeting ∼20,000 human genes, together with an ER stress cell model, we performed flow cytometry-based cell sorting to isolate cells with defective response to arsenite. Our screen discovered several genes modulating arsenite-induced ER stress, including sodium-dependent neutral amino acid transporter, SNAT2. SNAT2 expression and activity are up-regulated by arsenite, in a manner dependent on activating transcription factor 4 (ATF4), an important mediator of the integrated stress response. Inhibition of SNAT2 expression or activity or deprivation of its primary substrate, glutamine, specifically suppressed ER stress induced by arsenite but not tunicamycin. Induction of SNAT2 is coincident with the activation of the nutrient-sensing mammalian target of rapamycin (mTOR) pathway, which is at least partially required for arsenite-induced ER stress. Importantly, inhibition of the SNAT2 or the System L transporter, LAT1, suppressed mTOR activation by arsenite, supporting a role for these transporters in modulating amino acid signaling. These findings reveal SNAT2 as an important and specific mediator of arsenic-induced ER stress, and suggest a role for aberrant mTOR activation in arsenic-related human diseases. Furthermore, this study demonstrates the utility of RNAi screens in elucidating cellular mechanisms of environmental toxins.
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