Source:http://linkedlifedata.com/resource/pubmed/id/15944709
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7043
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pubmed:dateCreated |
2005-6-9
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pubmed:abstractText |
MicroRNAs (miRNAs) are 21-23 nucleotide RNA molecules that regulate the stability or translational efficiency of target messenger RNAs. miRNAs have diverse functions, including the regulation of cellular differentiation, proliferation and apoptosis. Although strict tissue- and developmental-stage-specific expression is critical for appropriate miRNA function, mammalian transcription factors that regulate miRNAs have not yet been identified. The proto-oncogene c-MYC encodes a transcription factor that regulates cell proliferation, growth and apoptosis. Dysregulated expression or function of c-Myc is one of the most common abnormalities in human malignancy. Here we show that c-Myc activates expression of a cluster of six miRNAs on human chromosome 13. Chromatin immunoprecipation experiments show that c-Myc binds directly to this locus. The transcription factor E2F1 is an additional target of c-Myc that promotes cell cycle progression. We find that expression of E2F1 is negatively regulated by two miRNAs in this cluster, miR-17-5p and miR-20a. These findings expand the known classes of transcripts within the c-Myc target gene network, and reveal a mechanism through which c-Myc simultaneously activates E2F1 transcription and limits its translation, allowing a tightly controlled proliferative signal.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/E2F Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/E2F1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/E2f1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/MicroRNAs,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1476-4687
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
435
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
839-43
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15944709-Animals,
pubmed-meshheading:15944709-Cell Cycle Proteins,
pubmed-meshheading:15944709-Cell Line,
pubmed-meshheading:15944709-Chromatin Immunoprecipitation,
pubmed-meshheading:15944709-Chromosomes, Human, Pair 13,
pubmed-meshheading:15944709-DNA-Binding Proteins,
pubmed-meshheading:15944709-E2F Transcription Factors,
pubmed-meshheading:15944709-E2F1 Transcription Factor,
pubmed-meshheading:15944709-Gene Expression Regulation,
pubmed-meshheading:15944709-Humans,
pubmed-meshheading:15944709-MicroRNAs,
pubmed-meshheading:15944709-Protein Binding,
pubmed-meshheading:15944709-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:15944709-Rats,
pubmed-meshheading:15944709-Transcription Factors
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pubmed:year |
2005
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pubmed:articleTitle |
c-Myc-regulated microRNAs modulate E2F1 expression.
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pubmed:affiliation |
Program in Human Genetics and Molecular Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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