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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...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The American Society for Cell Biology
2010
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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. |
format | Text |
id | pubmed-2947481 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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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