Source:http://linkedlifedata.com/resource/pubmed/id/19960022
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2010-2-15
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pubmed:abstractText |
E2F1 is a positive regulator of cell cycle progression and also a potent inducer of apoptosis, especially when activated by DNA damage. We identified E2F1-inducible microRNAs (miRNAs) by microarray hybridization and found that the levels of miRNAs 449a and 449b, as well as their host gene CDC20B, are strongly upregulated by E2F1. High miR-449 levels were found in testes, lung, and trachea, but not in testicular and other cancer cells. MiR-449a/b structurally resemble the p53-inducible miRNA 34 family. In agreement with a putative tumor-suppressive role, miR-449a as well as miR-34a reduced proliferation and strongly promoted apoptosis by at least partially p53-independent mechanisms. Both miRNAs reduced the levels of CDK6, implying miR-449 in a negative feedback mechanism for E2F1. Moreover, miR-449a and miR-34a diminished the deacetylase Sirt1 and augmented p53 acetylation. We propose that both miRNAs provide a twofold safety mechanism to avoid excessive E2F1-induced proliferation by cell cycle arrest and by apoptosis. While responding to different transactivators, miRNAs 449 and 34 each repress E2F1, but promote p53 activity, allowing efficient cross-talk between two major DNA damage-responsive gene regulators.
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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-Dependent Kinase 6,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN34 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MIRN449 microRNA, human,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/Sirtuins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1476-5403
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
452-8
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pubmed:meshHeading |
pubmed-meshheading:19960022-Apoptosis,
pubmed-meshheading:19960022-Cell Line, Tumor,
pubmed-meshheading:19960022-Cell Proliferation,
pubmed-meshheading:19960022-Cyclin-Dependent Kinase 6,
pubmed-meshheading:19960022-E2F1 Transcription Factor,
pubmed-meshheading:19960022-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:19960022-Humans,
pubmed-meshheading:19960022-MicroRNAs,
pubmed-meshheading:19960022-Microarray Analysis,
pubmed-meshheading:19960022-Sirtuins
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pubmed:year |
2010
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pubmed:articleTitle |
E2F1-inducible microRNA 449a/b suppresses cell proliferation and promotes apoptosis.
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pubmed:affiliation |
Department of Molecular Oncology, Göttingen Center of Molecular Biosciences -GZMB, Ernst Caspari Haus, University of Göttingen, Justus von Liebig Weg 11, 37077 Göttingen, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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