Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity.
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.
Division of Nephrology, Johns Hopkins School of Medicine, 963 Ross Building, 720 Rutland Avenue, Baltimore, MD 21205, USA.
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H
Miyakawa
S K
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Woo
S C
SC
Dahl
J S
JS
Handler
H M
HM
Kwon
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004285:Dogs; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D006982:Hypertonic Solutions; D007668:Kidney / Q000378:metabolism; D007679:Kidney Medulla / Q000502:physiology*; D008322:Mammals; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012462:Saline Solution, Hypertonic; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D006982:Hypertonic Solutions; C118125:NFAT5 protein, human; D011994:Recombinant Proteins; D012462:Saline Solution, Hypertonic; D015534:Trans-Activators; D014157:Transcription Factors