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TonEBP/NFAT5 stimulates transcription of HSP70 in response to hypertonicity.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2002 Aug; Vol. 22 (16), pp. 5753-60. - Publication Year :
- 2002
-
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.
- Subjects :
- 5' Flanking Region genetics
Animals
Cell Fractionation
Cell Line
Epithelial Cells cytology
Epithelial Cells metabolism
Exons genetics
Genes, Reporter
HSP70 Heat-Shock Proteins metabolism
Humans
Kidney Medulla cytology
Mice
Mice, Transgenic
NFATC Transcription Factors
Nuclear Proteins metabolism
Promoter Regions, Genetic
Protein Binding
Signal Transduction physiology
DNA-Binding Proteins metabolism
HSP70 Heat-Shock Proteins genetics
Osmotic Pressure
Transcription Factors metabolism
Transcription, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 0270-7306
- Volume :
- 22
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 12138186
- Full Text :
- https://doi.org/10.1128/MCB.22.16.5753-5760.2002