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Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor

Serum stimulation of mammalian cells induces, via the MAPK pathway, the nuclear protein DUSP5 (dual-specificity phosphatase 5), which specifically interacts with and inactivates the ERK1/2 MAP kinases. However, molecular mechanisms underlying DUSP5 induction are not well known. Here, we found that t...

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Autores principales: Buffet, Camille, Catelli, Maria-Grazia, Hecale-Perlemoine, Karine, Bricaire, Léopoldine, Garcia, Camille, Gallet-Dierick, Anne, Rodriguez, Stéphanie, Cormier, Françoise, Groussin, Lionel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687125/
https://www.ncbi.nlm.nih.gov/pubmed/26691724
http://dx.doi.org/10.1371/journal.pone.0145484
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author Buffet, Camille
Catelli, Maria-Grazia
Hecale-Perlemoine, Karine
Bricaire, Léopoldine
Garcia, Camille
Gallet-Dierick, Anne
Rodriguez, Stéphanie
Cormier, Françoise
Groussin, Lionel
author_facet Buffet, Camille
Catelli, Maria-Grazia
Hecale-Perlemoine, Karine
Bricaire, Léopoldine
Garcia, Camille
Gallet-Dierick, Anne
Rodriguez, Stéphanie
Cormier, Françoise
Groussin, Lionel
author_sort Buffet, Camille
collection PubMed
description Serum stimulation of mammalian cells induces, via the MAPK pathway, the nuclear protein DUSP5 (dual-specificity phosphatase 5), which specifically interacts with and inactivates the ERK1/2 MAP kinases. However, molecular mechanisms underlying DUSP5 induction are not well known. Here, we found that the DUSP5 mRNA induction depends on a transcriptional regulation by the MAPK pathway, without any modification of the mRNA stability. Two contiguous CArG boxes that bind serum response factor (SRF) were found in a 1 Kb promoter region, as well as several E twenty-six transcription factor family binding sites (EBS). These sites potentially bind Elk-1, a transcription factor activated by ERK1/2. Using wild type or mutated DUSP5 promoter reporters, we demonstrated that SRF plays a crucial role in serum induction of DUSP5 promoter activity, the proximal CArG box being important for SRF binding in vitro and in living cells. Moreover, in vitro and in vivo binding data of Elk-1 to the same promoter region further demonstrate a role for Elk-1 in the transcriptional regulation of DUSP5. SRF and Elk-1 form a ternary complex (Elk-1-SRF-DNA) on DUSP5 promoter, consequently providing a link to an important negative feedback tightly regulating phosphorylated ERK levels.
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spelling pubmed-46871252016-01-07 Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor Buffet, Camille Catelli, Maria-Grazia Hecale-Perlemoine, Karine Bricaire, Léopoldine Garcia, Camille Gallet-Dierick, Anne Rodriguez, Stéphanie Cormier, Françoise Groussin, Lionel PLoS One Research Article Serum stimulation of mammalian cells induces, via the MAPK pathway, the nuclear protein DUSP5 (dual-specificity phosphatase 5), which specifically interacts with and inactivates the ERK1/2 MAP kinases. However, molecular mechanisms underlying DUSP5 induction are not well known. Here, we found that the DUSP5 mRNA induction depends on a transcriptional regulation by the MAPK pathway, without any modification of the mRNA stability. Two contiguous CArG boxes that bind serum response factor (SRF) were found in a 1 Kb promoter region, as well as several E twenty-six transcription factor family binding sites (EBS). These sites potentially bind Elk-1, a transcription factor activated by ERK1/2. Using wild type or mutated DUSP5 promoter reporters, we demonstrated that SRF plays a crucial role in serum induction of DUSP5 promoter activity, the proximal CArG box being important for SRF binding in vitro and in living cells. Moreover, in vitro and in vivo binding data of Elk-1 to the same promoter region further demonstrate a role for Elk-1 in the transcriptional regulation of DUSP5. SRF and Elk-1 form a ternary complex (Elk-1-SRF-DNA) on DUSP5 promoter, consequently providing a link to an important negative feedback tightly regulating phosphorylated ERK levels. Public Library of Science 2015-12-21 /pmc/articles/PMC4687125/ /pubmed/26691724 http://dx.doi.org/10.1371/journal.pone.0145484 Text en © 2015 Buffet et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Buffet, Camille
Catelli, Maria-Grazia
Hecale-Perlemoine, Karine
Bricaire, Léopoldine
Garcia, Camille
Gallet-Dierick, Anne
Rodriguez, Stéphanie
Cormier, Françoise
Groussin, Lionel
Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor
title Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor
title_full Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor
title_fullStr Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor
title_full_unstemmed Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor
title_short Dual Specificity Phosphatase 5, a Specific Negative Regulator of ERK Signaling, Is Induced by Serum Response Factor and Elk-1 Transcription Factor
title_sort dual specificity phosphatase 5, a specific negative regulator of erk signaling, is induced by serum response factor and elk-1 transcription factor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687125/
https://www.ncbi.nlm.nih.gov/pubmed/26691724
http://dx.doi.org/10.1371/journal.pone.0145484
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