p38 MAPKs (mitogen-activated protein kinases) play important roles in the regulation of cellular responses to environmental stress. Recently, this signalling pathway has also been implicated in the regulation of processes unrelated to stress, for example, in T lymphocytes and cardiomyocytes. In order to identify molecular targets responsible for the housekeeping functions of p38 MAPKs, we have analysed the differences in the transcriptomes of normally proliferating wild-type and p38α knockout immortalized embryonic cardiomyocytes. Interestingly, many potential components of the myocardium extracellular matrix were found to be upregulated in the absence of p38α. Further analysis of the microarray data identified TEF-1 (transcriptional enhancer factor-1), a known regulator of heart-specific gene expression, and C/EBPβ (CCAAT/enhancer-binding protein β), as the two transcription factors the binding sites of which were most enriched in the promoters of p38α-regulated genes. We have focused on the study of the extracellular matrix component COL1A1 (α1 chain of type I collagen) and found evidence for the involvement of both TEF-1 and C/EBPβ in the p38α-dependent inhibition of COL1A1 transcription. Our data therefore show that p38 MAPKs regulate TEF-1 and C/EBPβ transcriptional activity in the absence of environmental stress and suggests a role for p38α in the expression of extracellular matrix components that maintain organ architecture.
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Research Article|
April 26 2006
TEF-1 and C/EBPβ are major p38α MAPK-regulated transcription factors in proliferating cardiomyocytes
Concetta Ambrosino;
Concetta Ambrosino
1
*European Molecular Biology Laboratory, 69117 Heidelberg, Germany
†Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, 80138 Napoli, Italy
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Tomoko Iwata;
‡Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology, 82152 Martinsried, Germany
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Claudio Scafoglio;
Claudio Scafoglio
†Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, 80138 Napoli, Italy
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Massimo Mallardo;
Massimo Mallardo
§Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli ‘Federico II’, Italy
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Rüdiger Klein;
Rüdiger Klein
‡Department of Molecular Neurobiology, Max-Planck Institute of Neurobiology, 82152 Martinsried, Germany
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Angel R. Nebreda
Angel R. Nebreda
3
*European Molecular Biology Laboratory, 69117 Heidelberg, Germany
∥CNIO (Spanish National Cancer Center), Melchor Fernández Almagro 3, E-28029 Madrid, Spain
3To whom correspondence should be addressed (email anebreda@cnio.es).
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Publisher: Portland Press Ltd
Received:
September 12 2005
Revision Received:
February 01 2006
Accepted:
February 21 2006
Accepted Manuscript online:
February 21 2006
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2006
Biochem J (2006) 396 (1): 163–172.
Article history
Received:
September 12 2005
Revision Received:
February 01 2006
Accepted:
February 21 2006
Accepted Manuscript online:
February 21 2006
Citation
Concetta Ambrosino, Tomoko Iwata, Claudio Scafoglio, Massimo Mallardo, Rüdiger Klein, Angel R. Nebreda; TEF-1 and C/EBPβ are major p38α MAPK-regulated transcription factors in proliferating cardiomyocytes. Biochem J 15 May 2006; 396 (1): 163–172. doi: https://doi.org/10.1042/BJ20051502
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