p38α MAPK (mitogen-activated protein kinase) plays an important tumour suppressor role, which is mediated by both its negative effect on cell proliferation and its pro-apoptotic activity. Surprisingly, most tumour suppressor mechanisms co-ordinated by p38α have been reported to occur at the post-translational level. This contrasts with the important role of p38α in the regulation of transcription and the profound changes in gene expression that normally occur during tumorigenesis. We have analysed whole-genome expression profiles of Ras-transformed wild-type and p38α-deficient cells and have identified 202 genes that are potentially regulated by p38α in transformed cells. Expression analysis has confirmed the regulation of these genes by p38α in tumours, and functional validation has identified several of them as probable mediators of the tumour suppressor effect of p38α on Ras-induced transformation. Interestingly, approx. 10% of the genes that are negatively regulated by p38α in transformed cells contribute to EGF (epidermal growth factor) receptor signalling. Our results suggest that inhibition of EGF receptor signalling by transcriptional targets of p38α is an important function of this signalling pathway in the context of tumour suppression.
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March 2011
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Research Article|
February 24 2011
Expression and functional validation of new p38α transcriptional targets in tumorigenesis
Aneta Swat;
Aneta Swat
*CNIO (Spanish National Cancer Centre), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
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Ignacio Dolado;
Ignacio Dolado
*CNIO (Spanish National Cancer Centre), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
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Ana Igea;
Ana Igea
†Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain
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Gonzalo Gomez-Lopez;
Gonzalo Gomez-Lopez
*CNIO (Spanish National Cancer Centre), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
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David G. Pisano;
David G. Pisano
*CNIO (Spanish National Cancer Centre), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
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Ana Cuadrado;
Ana Cuadrado
*CNIO (Spanish National Cancer Centre), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
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Angel R. Nebreda
Angel R. Nebreda
1
*CNIO (Spanish National Cancer Centre), Melchor Fernandez Almagro 3, 28029 Madrid, Spain
†Institute for Research in Biomedicine (IRB Barcelona), Baldiri Reixac 10, 08028 Barcelona, Spain
‡ICREA (Institució Catalana de Recerca i Estudis Avançats), 08010 Barcelona, Spain
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
September 02 2010
Revision Received:
January 04 2011
Accepted:
January 12 2011
Accepted Manuscript online:
January 12 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2011 Biochemical Society
2011
Biochem J (2011) 434 (3): 549–558.
Article history
Received:
September 02 2010
Revision Received:
January 04 2011
Accepted:
January 12 2011
Accepted Manuscript online:
January 12 2011
Citation
Aneta Swat, Ignacio Dolado, Ana Igea, Gonzalo Gomez-Lopez, David G. Pisano, Ana Cuadrado, Angel R. Nebreda; Expression and functional validation of new p38α transcriptional targets in tumorigenesis. Biochem J 15 March 2011; 434 (3): 549–558. doi: https://doi.org/10.1042/BJ20101410
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