Source:http://linkedlifedata.com/resource/pubmed/id/16575904
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2006-5-1
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| pubmed:abstractText |
Previous studies demonstrate that p16, a cyclin-dependent kinase inhibitor and a tumor suppressor, may inhibit matrix metalloproteinase-2 (MMP-2) expression in human cancer cells to suppress tumor invasion and metastasis. However, the detailed mechanism is still unclear. Our results show that p16 inhibits MMP-2 expression via transcriptional repression. Promoter deletion and mutation analysis indicates that p16 acts through the Sp1 transcription factor-binding site located between -72 and -64 bp region from the transcriptional start site of the human MMP-2 promoter to repress gene expression. DNA affinity precipitation assay (DAPA) and chromatin immuno-precipitation (CHIP) assay demonstrate that Sp1 proteins constitutively bind to this consensus sequence in vitro and in vivo. p16 attenuates Sp1 binding to the MMP-2 promoter to suppress gene transcription and overexpression of Sp1 may counteract p16-induced downregulation of MMP-2. CyclinA/CDK complex may directly phosphorylate Sp1 and enhance its DNA-binding activity. Thus, we investigated the effect of p16 on the interaction between cyclin A and Sp1. Our results indicate that p16 induces downregulation of cyclin A and CDK2, reduces the interaction between cyclin A and Sp1, and attenuates phosphorylation of Sp1. Ectoexpression of cyclin A counteracts p16-mediated inhibition of DNA binding of Sp1 and activates MMP-2 promoter activity and mRNA expression. Collectively, our results suggest that p16 suppresses MMP-2 by blocking Sp1-mediated gene transcription.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Sp1 Transcription Factor
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
0021-9541
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright 2006 Wiley-Liss, Inc.
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| pubmed:issnType |
Print
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| pubmed:volume |
208
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
246-52
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:16575904-Cyclin A,
pubmed-meshheading:16575904-Cyclin-Dependent Kinase Inhibitor p16,
pubmed-meshheading:16575904-Down-Regulation,
pubmed-meshheading:16575904-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:16575904-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16575904-Humans,
pubmed-meshheading:16575904-Immunoblotting,
pubmed-meshheading:16575904-Immunoprecipitation,
pubmed-meshheading:16575904-Lung Neoplasms,
pubmed-meshheading:16575904-Matrix Metalloproteinase 2,
pubmed-meshheading:16575904-Neoplasm Invasiveness,
pubmed-meshheading:16575904-Neoplasm Metastasis,
pubmed-meshheading:16575904-Neovascularization, Pathologic,
pubmed-meshheading:16575904-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:16575904-Promoter Regions, Genetic,
pubmed-meshheading:16575904-Protein Binding,
pubmed-meshheading:16575904-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:16575904-Sp1 Transcription Factor,
pubmed-meshheading:16575904-Transcription, Genetic,
pubmed-meshheading:16575904-Tumor Cells, Cultured
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| pubmed:year |
2006
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| pubmed:articleTitle |
p16 inhibits matrix metalloproteinase-2 expression via suppression of Sp1-mediated gene transcription.
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| pubmed:affiliation |
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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