Source:http://linkedlifedata.com/resource/pubmed/id/11504716
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
44
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pubmed:dateCreated |
2001-10-29
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pubmed:abstractText |
MEF, a recently identified member of the E74 family of ETS-related transcription factors, is a strong transcriptional activator of cytokine gene expression. Using a green fluorescent protein gene reporter plasmid regulated by an MEF-responsive promoter, we determined that the transcriptional activity of MEF is largely restricted to the G1 phase of the cell cycle. MEF-dependent transcription was suppressed by the expression of cyclin A but not by cyclin D or cyclin E. This effect was due to the kinase activity generated by cyclin A expression, as co-expression of the cyclin-dependent kinase inhibitors p21 or p27, or a dominant negative form of CDK2 (DNK2), abrogated the reduction of MEF transcriptional activity by cyclin A. Cyclin A-CDK2 phosphorylated MEF protein in vitro more efficiently than cyclin D-CDK4 or cyclin E-CDK2, and phosphorylation of MEF by cyclin A-CDK2 reduced its ability to bind DNA. We determined one site of phosphorylation by cyclin A-CDK2 at the C terminus of MEF, using mass-spectrometry; mutation of three serine or threonine residues in this region significantly reduced phosphorylation of MEF by cyclin A and reduced cyclin A-mediated suppression of its transactivating activity. These amino acid substitutions also reduced the restriction of MEF activity to G1. Phosphorylation of MEF by the cyclin A-CDK2 complex controls its transcriptional activity during the cell cycle, establishing a novel link between the ETS family of proteins and the cell cycle machinery.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
2
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
40528-36
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:11504716-Amino Acid Sequence,
pubmed-meshheading:11504716-Animals,
pubmed-meshheading:11504716-Base Sequence,
pubmed-meshheading:11504716-COS Cells,
pubmed-meshheading:11504716-Cyclin A,
pubmed-meshheading:11504716-DNA Primers,
pubmed-meshheading:11504716-DNA-Binding Proteins,
pubmed-meshheading:11504716-G1 Phase,
pubmed-meshheading:11504716-Molecular Sequence Data,
pubmed-meshheading:11504716-Phosphorylation,
pubmed-meshheading:11504716-Transcription, Genetic,
pubmed-meshheading:11504716-Transcription Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Cyclin A-dependent phosphorylation of the ETS-related protein, MEF, restricts its activity to the G1 phase of the cell cycle.
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pubmed:affiliation |
Laboratory of Molecular Aspects of Hematopoiesis, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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