ArticleMolecular and cellular biology2002
TonEBP/NFAT5 stimulates transcription of HSP70 in response to hypertonicity.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 201 citations in OpenAlex.
- Kv2.1/Kv8.2 Channels Regulate Fluid Homeostasis in the Outer Retina.bioRxiv : the preprint server for biology · 2026Article
- Dissecting hypertonicity- and NFAT5-dependent gene expression programs in mpkCCD cells.Physiological reports · 2026Article
- SLC6A6 imports taurine into mitochondria to sustain mitochondrial translation and tumour growth.Nature metabolism · 2026Article
- NFAT5 dictates crosstalk between intestinal epithelial regenerative capacity and microbiota in murine colitis models.The Journal of clinical investigation · 2025Article
- Direct ionic stress sensing and mitigation by the transcription factor NFAT5.Science advances · 2025Article
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- 'Aquaporin-omics': mechanisms of aquaporin-2 loss in polyuric disorders.The Journal of physiology · 2024Article
- The Significant Role of microRNAs in Gliomas Angiogenesis: A Particular Focus on Molecular Mechanisms and Opportunities for Clinical Application.Cellular and molecular neurobiology · 2023Review
- Direct ionic stress sensing and mitigation by the transcription factor NFAT5.bioRxiv : the preprint server for biology · 2023Article
- NFAT5 Restricts Bovine Herpesvirus 1 Productive Infection in MDBK Cell Cultures.Microbiology spectrum · 2023Article
- Neutral amino acid transporter SLC38A2 protects renal medulla from hyperosmolarity-induced ferroptosis.eLife · 2023Article
- TonEBP expression is essential in the IL-1β-induced migration and invasion of human A549 lung cancer cells.Oncology research · 2023Article
- The nuclear factor of activated T cells 5 (NFAT5) contributes to the renal corticomedullary differences in gene expression.Scientific reports · 2022Article
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- Review
- Abnormal NFAT5 Physiology in Duchenne Muscular Dystrophy Fibroblasts as a Putative Explanation for the Permanent Fibrosis Formation in Duchenne Muscular Dystrophy.International journal of molecular sciences · 2020Article
- NFAT5, which protects against hypertonicity, is activated by that stress via structuring of its intrinsically disordered domain.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- TonEBP-deficiency accelerates intervertebral disc degeneration underscored by matrix remodeling, cytoskeletal rearrangements, and changes in proinflammatory gene expression.Matrix biology : journal of the International Society for Matrix Biology · 2020Article
- Article
- Autophagy and Hsp70 activation alleviate oral epithelial cell death induced by food-derived hypertonicity.Cell stress & chaperones · 2020Article
33 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
While hyperosmolality of the kidney medulla is essential for urinary concentration, it imposes a great deal of stress. Cells in the renal medulla adapt to the stress of hypertonicity (hyperosmotic salt) by accumulating organic osmolytes. Tonicity-responsive enhancer (TonE) binding protein (TonEBP) (or NFAT5) stimulates transcription of transporters and a synthetic enzyme for the cellular accumulation of organic osmolytes. We found that dominant-negative TonEBP reduced expression of HSP70 as well as the transporters and enzyme. Near the major histocompatibility complex class III locus, there are three HSP70 genes named HSP70-1, HSP70-2, and HSC70t. While HSP70-1 and HSP70-2 were heat inducible, only HSP70-2 was induced by hypertonicity. In the 5' flanking region of the HSP70-2 gene, there are three sites for TonEBP binding. In cells transfected with a reporter plasmid containing this region, expression of luciferase was markedly stimulated in response to hypertonicity. Coexpression of the dominant-negative TonEBP reduced the luciferase expression. Mutating all three sites in the reporter plasmid led to a complete loss of induction by hypertonicity. Thus, TonEBP rather than heat shock factor stimulates transcription of the HSP70-2 gene in response to hypertonicity. We conclude that TonEBP is a master regulator of the renal medulla for cellular protection against high osmolality via organic osmolytes and molecular chaperones.
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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.