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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-5-23
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pubmed:abstractText |
Activation of p38 MAPK has been shown to be relevant for a number of bone morphogenetic protein (BMP) physiological effects. We report here the involvement of noncanonical phosphorylated mothers against decapentaplegic (Smad) signaling in the transcriptional induction of Cox2 (Ptgs2) by BMP-2 in mesenchymal cells and organotypic calvarial cultures. We demonstrate that different regulatory elements are required for regulation of Cox2 expression by BMP-2: Runt-related transcription factor-2 and cAMP response element sites are essential, whereas a GC-rich Smad binding element is important for full responsiveness. Efficient transcriptional activation requires cooperation between transcription factors because mutation of any element results in a strong decrease of BMP-2 responsiveness. BMP-2 activation of p38 leads to increased recruitment of activating transcription factor-2, Runx2, Smad, and coactivators such as p300 at the responsive sites in the Cox2 proximal promoter. We demonstrate, by either pharmacological or genetic analysis, that maximal BMP-2 effects on Cox2 and JunB expression require the function of p38 and its downstream effector mitogen/stress-activated kinase 1. Altogether our results strongly suggest that cooperative effects between canonical and noncanonical BMP signaling allow the fine-tuning of BMP transcriptional responses on specific target genes.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/(6-(4-(2-piperidin-1-ylethoxy)phenyl...,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 1 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrimidines,
http://linkedlifedata.com/resource/pubmed/chemical/Runx2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1944-9917
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1006-17
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pubmed:meshHeading |
pubmed-meshheading:21436263-Animals,
pubmed-meshheading:21436263-Bone Morphogenetic Protein 2,
pubmed-meshheading:21436263-Cell Line,
pubmed-meshheading:21436263-Core Binding Factor Alpha 1 Subunit,
pubmed-meshheading:21436263-Cyclooxygenase 2,
pubmed-meshheading:21436263-Enzyme Inhibitors,
pubmed-meshheading:21436263-Gene Expression Regulation,
pubmed-meshheading:21436263-Imidazoles,
pubmed-meshheading:21436263-Mesenchymal Stem Cells,
pubmed-meshheading:21436263-Mice,
pubmed-meshheading:21436263-Promoter Regions, Genetic,
pubmed-meshheading:21436263-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:21436263-Pyrazoles,
pubmed-meshheading:21436263-Pyridines,
pubmed-meshheading:21436263-Pyrimidines,
pubmed-meshheading:21436263-Regulatory Elements, Transcriptional,
pubmed-meshheading:21436263-Response Elements,
pubmed-meshheading:21436263-Signal Transduction,
pubmed-meshheading:21436263-Skull,
pubmed-meshheading:21436263-Tissue Culture Techniques,
pubmed-meshheading:21436263-Transcription, Genetic,
pubmed-meshheading:21436263-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2011
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pubmed:articleTitle |
Noncanonical BMP signaling regulates cyclooxygenase-2 transcription.
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pubmed:affiliation |
Departament de Ciències Fisiològiques II, Bellvitge Biomedical Research Institute, C/ Feixa Llarga s/n., L'Hospitalet de Llobregat, Universitat de Barcelona, E-08907 Barcelona, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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