BROWSE

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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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Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-kappa B Activity

Cited 26 times inthomson ciCited 18 times inthomson ci
Title
Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-kappa B Activity
Author
Roth, IsabelleLeroy, ValerieKwon, H. MooMartin, Pierre-YvesFeraille, EricHasler, Udo
Keywords
DUCT PRINCIPAL CELLS; OSMOTIC RESPONSE ELEMENT; ENHANCER-BINDING PROTEIN; SMOOTH-MUSCLE-CELLS; GROWTH-FACTOR-C; HIGH NACL; GENE-TRANSCRIPTION; AQUAPORIN-2 EXPRESSION; FACTOR TONEBP/OREBP; HYPERTONIC STRESS
Issue Date
201010
Publisher
AMER SOC CELL BIOLOGY
Citation
MOLECULAR BIOLOGY OF THE CELL, v.21, no.19, pp.3459 - 3474
Abstract
Tonicity-responsive binding-protein (TonEBP or NFAT5) is a widely expressed transcription factor whose activity is regulated by extracellular tonicity. TonEBP plays a key role in osmoprotection by binding to osmotic response element/TonE elements of genes that counteract the deleterious effects of cell shrinkage. Here, we show that in addition to this "classical" stimulation, TonEBP protects cells against hypertonicity by enhancing nuclear factor-kappa B (NF-kappa B) activity. We show that hypertonicity enhances NF-kappa B stimulation by lipopolysaccharide but not tumor necrosis factor-alpha, and we demonstrate overlapping protein kinase B (Akt)-dependent signal transduction pathways elicited by hypertonicity and transforming growth factor-alpha. Activation of p38 kinase by hypertonicity and downstream activation of Akt play key roles in TonEBP activity, I kappa B alpha degradation, and p65 nuclear translocation. TonEBP affects neither of these latter events and is itself insensitive to NF-kappa B signaling. Rather, we reveal a tonicity-dependent interaction between TonEBP and p65 and show that NF-kappa B activity is considerably enhanced after binding of NF-kappa B-TonEBP complexes to kappa B elements of NF-kappa B-responsive genes. We demonstrate the key roles of TonEBP and Akt in renal collecting duct epithelial cells and in macrophages. These findings reveal a novel role for TonEBP and Akt in NF-kappa B activation on the onset of hypertonic challenge.
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DOI
http://dx.doi.org/10.1091/mbc.E10-02-0133
ISSN
1059-1524
Appears in Collections:
SLS_Journal Papers
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