ArticleProceedings of the National Academy of Sciences of the United States of America2004
ATM, a DNA damage-inducible kinase, contributes to activation by high NaCl of the transcription factor TonEBP/OREBP.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 108 citations in OpenAlex.
- HES1 potentiates high salt stress response as an enhancer of NFAT5-DNA binding.Communications biology · 2024Article
- The enhancer RNA, AANCR, regulates APOE expression in astrocytes and microglia.Nucleic acids research · 2024Article
- NFAT5 Restricts Bovine Herpesvirus 1 Productive Infection in MDBK Cell Cultures.Microbiology spectrum · 2023Article
- Stress Factors as Possible Regulators of Pluripotent Stem Cell Survival and Differentiation.Biology · 2023Review
- Elucidation of the Molecular Pathways Involved in the Protective Effects of AUY-922 in LPS-Induced Inflammation in Mouse Lungs.Pharmaceuticals (Basel, Switzerland) · 2021Article
- NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction.International journal of molecular sciences · 2021Review
- Urinary Extracellular Vesicles as a Source of NGAL for Diabetic Kidney Disease Evaluation in Children and Adolescents With Type 1 Diabetes Mellitus.Frontiers in endocrinology · 2021Article
- The evolving role of TonEBP as an immunometabolic stress protein.Nature reviews. Nephrology · 2020Review
- Potential Role of Gene Regulator NFAT5 in the Pathogenesis of Diabetes Mellitus.Journal of diabetes research · 2020Review
- SOX17 overexpression sensitizes chemoradiation response in esophageal cancer by transcriptional down-regulation of DNA repair and damage response genes.Journal of biomedical science · 2019Article
- Regulation of Inflammatory Functions of Macrophages and T Lymphocytes by NFAT5.Frontiers in immunology · 2019Review
- NFAT5 Isoform C Controls Biomechanical Stress Responses of Vascular Smooth Muscle Cells.Frontiers in physiology · 2018Article
- Context-dependent regulation of Th17-associated genes and IFNγ expression by the transcription factor NFAT5.Immunology and cell biology · 2017Article
- Peptide affinity analysis of proteins that bind to an unstructured region containing the transactivating domain of the osmoprotective transcription factor NFAT5.Physiological genomics · 2016Article
- Peptide affinity analysis of proteins that bind to an unstructured NH2-terminal region of the osmoprotective transcription factor NFAT5.Physiological genomics · 2016Article
- How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?World journal of nephrology · 2016Review
- High concentrations of NaCl induce cell swelling leading to senescence in human cells.Molecular and cellular biochemistry · 2016Article
- Mechanistic heterogeneity in site recognition by the structurally homologous DNA-binding domains of the ETS family transcription factors Ets-1 and PU.1.The Journal of biological chemistry · 2014Article
- Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats.World journal of hepatology · 2014Article
- Macrophages in homeostatic immune function.Frontiers in physiology · 2014Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
High NaCl activates the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP), resulting in increased transcription of several protective genes, including the glycine betaine/gamma-aminobutyric acid transporter (BGT1). High NaCl damages DNA, and DNA damage activates ataxia telangiectasia mutated (ATM) kinase through autophosphorylation on Ser-1981. TonEBP/OREBP contains ATM consensus phosphorylation sites at Ser-1197, Ser-1247, and Ser-1367. The present studies test whether ATM is involved in activation of TonEBP/OREBP by high NaCl. We find that raising osmolality from 300 to 500 mosmol/kg by adding NaCl activates ATM, as indicated by phosphorylation at Ser-1981. High urea and radiation also activate ATM, but they do not increase TonEBP/OREBP transcriptional activity like high NaCl does. Wortmannin, which inhibits ATM, reduces NaCl-induced TonEBP/OREBP transcriptional activation and BGT1 mRNA increase. Overexpression of wild-type TonEBP/OREBP increases ORE/TonE reporter activity much more than does overexpression of TonEBP/OREBP S1197A, S1247A, or S1367A. In AT cells (which express nonfunctional ATM), TonEBP/OREBP transcriptional and transactivating activity are further increased by expression of wild-type ATM but not of S1981A ATM. TonEBP/OREBP reciprocally coimmunoprecipitates with ATM kinase, demonstrating physical association. Additionally, antibody to ATM kinase supershifts TonEBP/OREBP bound to its cognate ORE/TonE DNA element. In AT cells, wortmannin further decreases high NaCl-induced increase in transcriptional activity, consistent with participation of signaling kinase(s) in addition to ATM. In conclusion, signaling via ATM is necessary for full activation of TonEBP/OREBP by high NaCl, but it is not sufficient.
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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.