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Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity

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 c...

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Autores principales: Roth, Isabelle, Leroy, Valérie, Kwon, H. Moo, Martin, Pierre-Yves, Féraille, Eric, Hasler, Udo
Formato: Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947481/
https://www.ncbi.nlm.nih.gov/pubmed/20685965
http://dx.doi.org/10.1091/mbc.E10-02-0133
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author Roth, Isabelle
Leroy, Valérie
Kwon, H. Moo
Martin, Pierre-Yves
Féraille, Eric
Hasler, Udo
author_facet Roth, Isabelle
Leroy, Valérie
Kwon, H. Moo
Martin, Pierre-Yves
Féraille, Eric
Hasler, Udo
author_sort Roth, Isabelle
collection PubMed
description 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-κB (NF-κB) activity. We show that hypertonicity enhances NF-κB stimulation by lipopolysaccharide but not tumor necrosis factor-α, and we demonstrate overlapping protein kinase B (Akt)-dependent signal transduction pathways elicited by hypertonicity and transforming growth factor-α. Activation of p38 kinase by hypertonicity and downstream activation of Akt play key roles in TonEBP activity, IκBα degradation, and p65 nuclear translocation. TonEBP affects neither of these latter events and is itself insensitive to NF-κB signaling. Rather, we reveal a tonicity-dependent interaction between TonEBP and p65 and show that NF-κB activity is considerably enhanced after binding of NF-κB-TonEBP complexes to κB elements of NF-κB–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-κB activation on the onset of hypertonic challenge.
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spelling pubmed-29474812010-12-16 Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity Roth, Isabelle Leroy, Valérie Kwon, H. Moo Martin, Pierre-Yves Féraille, Eric Hasler, Udo Mol Biol Cell Articles 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-κB (NF-κB) activity. We show that hypertonicity enhances NF-κB stimulation by lipopolysaccharide but not tumor necrosis factor-α, and we demonstrate overlapping protein kinase B (Akt)-dependent signal transduction pathways elicited by hypertonicity and transforming growth factor-α. Activation of p38 kinase by hypertonicity and downstream activation of Akt play key roles in TonEBP activity, IκBα degradation, and p65 nuclear translocation. TonEBP affects neither of these latter events and is itself insensitive to NF-κB signaling. Rather, we reveal a tonicity-dependent interaction between TonEBP and p65 and show that NF-κB activity is considerably enhanced after binding of NF-κB-TonEBP complexes to κB elements of NF-κB–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-κB activation on the onset of hypertonic challenge. The American Society for Cell Biology 2010-10-01 /pmc/articles/PMC2947481/ /pubmed/20685965 http://dx.doi.org/10.1091/mbc.E10-02-0133 Text en © 2010 by The American Society for Cell Biology This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution-Noncommercial-Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).
spellingShingle Articles
Roth, Isabelle
Leroy, Valérie
Kwon, H. Moo
Martin, Pierre-Yves
Féraille, Eric
Hasler, Udo
Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity
title Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity
title_full Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity
title_fullStr Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity
title_full_unstemmed Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity
title_short Osmoprotective Transcription Factor NFAT5/TonEBP Modulates Nuclear Factor-κB Activity
title_sort osmoprotective transcription factor nfat5/tonebp modulates nuclear factor-κb activity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2947481/
https://www.ncbi.nlm.nih.gov/pubmed/20685965
http://dx.doi.org/10.1091/mbc.E10-02-0133
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