Document Detail

Cyclin A-dependent phosphorylation of the ETS-related protein, MEF, restricts its activity to the G1 phase of the cell cycle.
MedLine Citation:
PMID:  11504716     Owner:  NLM     Status:  MEDLINE    
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.
Y Miyazaki; P Boccuni; S Mao; J Zhang; H Erdjument-Bromage; P Tempst; H Kiyokawa; S D Nimer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.     Date:  2001-08-14
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  276     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-29     Completed Date:  2001-12-07     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  40528-36     Citation Subset:  IM    
Laboratory of Molecular Aspects of Hematopoiesis, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
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MeSH Terms
Amino Acid Sequence
Base Sequence
COS Cells
Cyclin A / metabolism*
DNA Primers
DNA-Binding Proteins / chemistry,  metabolism*,  physiology
G1 Phase / physiology*
Molecular Sequence Data
Transcription Factors / chemistry,  metabolism*,  physiology
Transcription, Genetic
Grant Support
Reg. No./Substance:
0/Cyclin A; 0/DNA Primers; 0/DNA-Binding Proteins; 0/Transcription Factors

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