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Text
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URL Address
<a href="http://doi.org/10.1074/jbc.M502751200" target="_blank" rel="noreferrer noopener">http://doi.org/10.1074/jbc.M502751200</a>
Pages
30517–30525
Issue
34
Volume
280
Dublin Core
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Title
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Bcl-2 positively regulates Sox9-dependent chondrocyte gene expression by suppressing the MEK-ERK1/2 signaling pathway.
Publisher
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The Journal of biological chemistry
Date
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2005
2005-08
Subject
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*Gene Expression Regulation; Adenoviridae/genetics; Animals; Apoptosis; beta-Galactosidase/metabolism; Blotting; Butadienes/pharmacology; Caspase Inhibitors; Cell Differentiation; Cell Line; Chondrocytes/*metabolism; Collagen Type II/metabolism; Down-Regulation; Enzyme Inhibitors/pharmacology; Fibroblasts/metabolism; Fluorescence; Genetic; High Mobility Group Proteins/*metabolism; Lac Operon; Luciferases/metabolism; MAP Kinase Kinase Kinases/*metabolism; Messenger/metabolism; Microscopy; Mitogen-Activated Protein Kinase 1/*metabolism; Mitogen-Activated Protein Kinase 3/*metabolism; NF-kappa B/metabolism; Nitriles/pharmacology; Phenotype; Phosphorylation; Promoter Regions; Protein Kinase C-alpha; Protein Kinase C/antagonists & inhibitors; Proteoglycans/metabolism; Proto-Oncogene Proteins c-bcl-2/*metabolism; Rats; Reverse Transcriptase Polymerase Chain Reaction; RNA; Signal Transduction; Small Interfering/metabolism; SOX9 Transcription Factor; Sprague-Dawley; Time Factors; Transcription; Transcription Factors/*metabolism; Transfection; Western
Creator
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Yagi Rieko; McBurney Denise; Horton Walter E Jr
Description
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Bcl-2 is an anti-apoptotic protein that has recently been shown to regulate other cellular functions. We previously reported that Bcl-2 regulates chondrocyte matrix gene expression, independent of its anti-apoptotic function. Here, we further investigate this novel function of Bcl-2 and examine three intracellular signaling pathways likely to be associated with this function. The present study demonstrates that the activity of Sox9, a master transcription factor that regulates the gene expression of chondrocyte matrix proteins, is suppressed by Bcl-2 small interference RNA in the presence of caspase inhibitors. This effect was attenuated by prior exposure of chondrocytes to an adenoviral vector expressing sense Bcl-2. In addition, the down-regulation of Bcl-2, Sox9, and chondrocyte-specific gene expression by serum withdrawal in primary chondrocytes was reversed by expressing Bcl-2. Inhibition of the protein kinase C alpha and NFkappaB pathways had no effect on the maintenance of Sox9-dependent gene expression by Bcl-2. In contrast, whereas the MEK-ERK1/2 pathway negatively regulated the differentiated phenotype in wild type chondrocytes, inhibition of this pathway reversed the loss of differentiation markers and fibroblastic phenotype in Bcl-2-deficient chondrocytes. In conclusion, the present study identifies a specific signaling pathway, namely, MEK-ERK1/2, that is downstream of Bcl-2 in the regulation of Sox9-dependent chondrocyte gene expression and phenotype.
Identifier
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<a href="http://doi.org/10.1074/jbc.M502751200" target="_blank" rel="noreferrer noopener">10.1074/jbc.M502751200</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Gene Expression Regulation
2005
Adenoviridae/genetics
Animals
Apoptosis
beta-Galactosidase/metabolism
Blotting
Butadienes/pharmacology
Caspase Inhibitors
Cell Differentiation
Cell Line
Chondrocytes/*metabolism
Collagen Type II/metabolism
Department of Anatomy & Neurobiology
Down-Regulation
Enzyme Inhibitors/pharmacology
Fibroblasts/metabolism
Fluorescence
Genetic
High Mobility Group Proteins/*metabolism
Horton Walter E Jr
Lac Operon
Luciferases/metabolism
MAP Kinase Kinase Kinases/*metabolism
McBurney Denise
Messenger/metabolism
Microscopy
Mitogen-Activated Protein Kinase 1/*metabolism
Mitogen-Activated Protein Kinase 3/*metabolism
NEOMED College of Medicine
NF-kappa B/metabolism
Nitriles/pharmacology
Phenotype
Phosphorylation
Promoter Regions
Protein Kinase C-alpha
Protein Kinase C/antagonists & inhibitors
Proteoglycans/metabolism
Proto-Oncogene Proteins c-bcl-2/*metabolism
Rats
Reverse Transcriptase Polymerase Chain Reaction
RNA
Signal Transduction
Small Interfering/metabolism
SOX9 Transcription Factor
Sprague-Dawley
The Journal of biological chemistry
Time Factors
Transcription
Transcription Factors/*metabolism
Transfection
Western
Yagi Rieko