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Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes
Myocyte Stress Protein 1 (MS1) is a muscle-specific, stress-responsive, regulator of gene expression. It was originally identified in embryonic mouse heart which showed increased expression in a rat model of left ventricular hypertrophy. To determine if MS1 was responsive to other stresses relevant...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ubiquity Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853832/ https://www.ncbi.nlm.nih.gov/pubmed/30210579 http://dx.doi.org/10.5334/1750-2187-12-3 |
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author | Hay, Joanna M. Jordan, Eva S. Browne, Gareth J. Bottrill, Andrew R. Prigent, Sally A. Dickens, Martin |
author_facet | Hay, Joanna M. Jordan, Eva S. Browne, Gareth J. Bottrill, Andrew R. Prigent, Sally A. Dickens, Martin |
author_sort | Hay, Joanna M. |
collection | PubMed |
description | Myocyte Stress Protein 1 (MS1) is a muscle-specific, stress-responsive, regulator of gene expression. It was originally identified in embryonic mouse heart which showed increased expression in a rat model of left ventricular hypertrophy. To determine if MS1 was responsive to other stresses relevant to cardiac myocyte function, we tested if it could be induced by the metabolic stresses associated with ischaemia/reperfusion injury in cardiac myocytes. We found that metabolic stress increased MS1 expression, both at the mRNA and protein level, concurrent with activation of the c-Jun N-terminal Kinase (JNK) signalling pathway. MS1 induction by metabolic stress was blocked by both the transcription inhibitor actinomycin D and a JNK inhibitor, suggesting that activation of the JNK pathway during metabolic stress in cardiac myocytes leads to transcriptional induction of MS1. MS1 was also found to be an efficient JNK substrate in vitro, with a major JNK phosphorylation site identified at Thr-62. In addition, MS1 was found to co-precipitate with JNK, and inspection of the amino acid sequence upstream of the phosphorylation site, at Thr-62, revealed a putative Mitogen-Activated Protein Kinase (MAPK) binding site. Taken together, these data identify MS1 as a likely transcriptional and post-translational target for the JNK pathway in cardiac myocytes subjected to metabolic stress. |
format | Online Article Text |
id | pubmed-5853832 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Ubiquity Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58538322018-03-27 Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes Hay, Joanna M. Jordan, Eva S. Browne, Gareth J. Bottrill, Andrew R. Prigent, Sally A. Dickens, Martin J Mol Signal Research Article Myocyte Stress Protein 1 (MS1) is a muscle-specific, stress-responsive, regulator of gene expression. It was originally identified in embryonic mouse heart which showed increased expression in a rat model of left ventricular hypertrophy. To determine if MS1 was responsive to other stresses relevant to cardiac myocyte function, we tested if it could be induced by the metabolic stresses associated with ischaemia/reperfusion injury in cardiac myocytes. We found that metabolic stress increased MS1 expression, both at the mRNA and protein level, concurrent with activation of the c-Jun N-terminal Kinase (JNK) signalling pathway. MS1 induction by metabolic stress was blocked by both the transcription inhibitor actinomycin D and a JNK inhibitor, suggesting that activation of the JNK pathway during metabolic stress in cardiac myocytes leads to transcriptional induction of MS1. MS1 was also found to be an efficient JNK substrate in vitro, with a major JNK phosphorylation site identified at Thr-62. In addition, MS1 was found to co-precipitate with JNK, and inspection of the amino acid sequence upstream of the phosphorylation site, at Thr-62, revealed a putative Mitogen-Activated Protein Kinase (MAPK) binding site. Taken together, these data identify MS1 as a likely transcriptional and post-translational target for the JNK pathway in cardiac myocytes subjected to metabolic stress. Ubiquity Press 2017-12-08 /pmc/articles/PMC5853832/ /pubmed/30210579 http://dx.doi.org/10.5334/1750-2187-12-3 Text en Copyright: © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Article Hay, Joanna M. Jordan, Eva S. Browne, Gareth J. Bottrill, Andrew R. Prigent, Sally A. Dickens, Martin Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes |
title | Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes |
title_full | Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes |
title_fullStr | Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes |
title_full_unstemmed | Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes |
title_short | Transcriptional and Post-Translational Targeting of Myocyte Stress Protein 1 (MS1) by the JNK Pathway in Cardiac Myocytes |
title_sort | transcriptional and post-translational targeting of myocyte stress protein 1 (ms1) by the jnk pathway in cardiac myocytes |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5853832/ https://www.ncbi.nlm.nih.gov/pubmed/30210579 http://dx.doi.org/10.5334/1750-2187-12-3 |
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