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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-1-23
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pubmed:abstractText |
How mitogens reduce the abundance of the cell cycle inhibitor p27(Kip1) is an important question, and regulation of p27(Kip1) translation and turnover has been described. Here we show that platelet-derived growth factor (PDGF) reduces the activity of the p27(Kip1) promoter and the abundance of the p27(Kip1) transcript in density-arrested mouse fibroblasts. Inhibition of p27(Kip1) gene expression by PDGF required protein synthesis and histone deacetylase activity but not Akt or ERK activity. PDGF increased the expression of c-Myc in the absence but not presence of a histone deacetylase inhibitor, and c-Myc inhibited p27(Kip1) promoter activity when ectopically expressed in fibroblasts. c-Myc targeted the same region of the p27(Kip1) promoter as did PDGF (deletion analysis) and interacted with this region in vivo (chromatin immunoprecipitation assay). Collectively, these findings suggest that c-Myc mediates the inhibitory effects of PDGF on the p27(Kip1) promoter. We also demonstrate reductions in p27(Kip1) mRNA abundance in primary splenocytes exposed to concanavalin A and in T cells exposed to interleukin-2 (IL-2). In contrast to PDGF in fibroblasts, IL-2 required Akt activity for maximal reductions in p27(Kip1) promoter activity and mRNA abundance in T cells. Thus, mitogens repress p27(Kip1) gene transcription in multiple systems and by multiple mechanisms.
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pubmed:grant |
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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/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Histone Deacetylases,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxamic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogens,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Platelet-Derived Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/trichostatin A
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1551-4005
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
115-24
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19158484-Animals,
pubmed-meshheading:19158484-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:19158484-Fibroblasts,
pubmed-meshheading:19158484-Gene Expression Regulation,
pubmed-meshheading:19158484-Histone Deacetylases,
pubmed-meshheading:19158484-Hydroxamic Acids,
pubmed-meshheading:19158484-Mice,
pubmed-meshheading:19158484-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:19158484-Mitogens,
pubmed-meshheading:19158484-NIH 3T3 Cells,
pubmed-meshheading:19158484-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:19158484-Platelet-Derived Growth Factor,
pubmed-meshheading:19158484-Promoter Regions, Genetic,
pubmed-meshheading:19158484-Protein Kinase Inhibitors,
pubmed-meshheading:19158484-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:19158484-RNA, Messenger,
pubmed-meshheading:19158484-RNA Stability,
pubmed-meshheading:19158484-T-Lymphocytes,
pubmed-meshheading:19158484-Transcription, Genetic
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pubmed:year |
2009
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pubmed:articleTitle |
Inhibition of p27Kip1 gene transcription by mitogens.
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pubmed:affiliation |
Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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