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Author

Kwon, H. Moo
Inflammation and Kidney Disorder Lab
Research Interests
  • TonEBP, Obesity, Cancer, Chronic inflammatory diseases, Brain disorder, Kidney disorders, Genomic instability

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Tonicity-responsive enhancer binding protein, a Rel-like protein that stimulates transcription in response to hypertonicity

Cited 323 times inthomson ciCited 305 times inthomson ci
Title
Tonicity-responsive enhancer binding protein, a Rel-like protein that stimulates transcription in response to hypertonicity
Author
Miyakawa, HWoo, SKDahl, SCHandler, JSKwon, H. Moo
Keywords
ALDOSE REDUCTASE GENE; INOSITOL COTRANSPORTER; MOLECULAR-CLONING; OSMOTIC-STRESS; DNA-BINDING; EXPRESSION; ACTIVATION; PHOSPHORYLATION; DEHYDROGENASE; REPRESSION
Issue Date
199903
Publisher
NATL ACAD SCIENCES
Citation
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.96, no.5, pp.2538 - 2542
Abstract
Hypertonicity (most often present as high salinity) is stressful to the cells of virtually all organisms. Cells survive in a hypertonic environment by increasing the transcription of genes whose products catalyze cellular accumulation of compatible osmolytes. In mammals, the kidney medulla is normally hypertonic because of the urinary concentrating mechanism. Cellular accumulation of compatible osmolytes in the renal medulla is catalyzed by the sodium/ myo-inositol cotransporter (SMIT), the sodium/chloride/ betaine cotransporter, and aldose reductase (synthesis of sorbitol). The importance of compatible osmolytes is underscored by the necrotic injury of the renal medulla and subsequent renal failure that results from the inhibition of SMIT in vivo by administration of a specific inhibitor. Tonicity-responsive enhancers (TonE) play a key role in hypertonicity-induced transcriptional stimulation of SMIT, sodium/ chloride/betaine cotransporter, and aldose reductase. We report the cDNA cloning of human TonE binding protein (TonEBP), a transcription factor that stimulates transcription through its binding to TonE; sequences via a Rel-like DNA binding domain. Western blot and immunohistochemical analyses of cells cultured in hypertonic medium reveal that exposure to hypertonicity elicits slow activation of TonEBP, which is the result of an increase in TonEBP amount and translocation to the nucleus.
URI
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DOI
http://dx.doi.org/10.1073/pnas.96.5.2538
ISSN
0027-8424
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