Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782406567416561664 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4687125 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT buffetcamille dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT catellimariagrazia dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT hecaleperlemoinekarine dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT bricaireleopoldine dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT garciacamille dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT galletdierickanne dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT rodriguezstephanie dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT cormierfrancoise dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor AT groussinlionel dualspecificityphosphatase5aspecificnegativeregulatoroferksignalingisinducedbyserumresponsefactorandelk1transcriptionfactor |