Document Detail


Cyclin A is a c-Jun target gene and is necessary for c-Jun-induced anchorage-independent growth in RAT1a cells.
MedLine Citation:
PMID:  15737994     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Overexpression of c-Jun enables Rat1a cells to grow in an anchorage-independent manner. We used an inducible c-Jun system under the regulation of doxycycline in Rat1a cells to identify potential c-Jun target genes necessary for c-Jun-induced anchorage-independent growth. Induction of c-Jun results in sustained expression of cyclin A in the nonadherent state with only minimal expression in the absence of c-Jun. The promoter activity of cyclin A2 was 4-fold higher in Rat1a cells in which c-Jun expression was induced compared with the control cells. Chromatin immunoprecipitation demonstrated that c-Jun bound directly to the cyclin A2 promoter. Mutation analysis of the cyclin A2 promoter mapped the c-Jun regulatory site to an ATF site at position -80. c-Jun was able to bind to this site both in vitro and in vivo, and mutation of this site completely abolished promoter activity. Cyclin A1 was also elevated in c-Jun-overexpressing Rat1a cells; however, c-Jun did not regulate this gene directly, since it did not bind directly to the cyclin A1 promoter. Suppression of cyclin A expression via the introduction of a cyclin A antisense sequences significantly reduced the ability of c-Jun-overexpressing Rat1a cells to grow in an anchorage-independent fashion. Taken together, these results suggest that cyclin A is a target of c-Jun and is necessary but not sufficient for c-Jun-induced anchorage-independent growth. In addition, we demonstrated that the cytoplasmic oncogenes Ras and Src transcriptionally activated the cyclin A2 promoter via the ATF site at position -80. Using a dominant negative c-Jun mutant, TAM67, we showed that this transcriptional activation of cyclin A2 requires c-Jun. Thus, our results suggest that c-Jun is a mediator of the aberrant cyclin A2 expression associated with Ras/Src-induced transformation.
Authors:
Motoo Katabami; Howard Donninger; Fumihiro Hommura; Virna D Leaner; Ichiro Kinoshita; Jeffrey F B Chick; Michael J Birrer
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Publication Detail:
Type:  Journal Article     Date:  2005-02-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  280     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-04-25     Completed Date:  2005-06-21     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  16728-38     Citation Subset:  IM    
Affiliation:
Department of Cell and Cancer Biology, NCI, National Institutes of Health, Rockville, Maryland 20850, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Binding Sites
Blotting, Western
Cell Adhesion
Cell Cycle
Cell Line, Transformed
Cell Line, Tumor
Cell Proliferation
Chromatin Immunoprecipitation
Cyclin A / chemistry,  metabolism,  physiology*
Cyclin A2
Cytoplasm / metabolism
DNA Mutational Analysis
Doxycycline / pharmacology
Genes, Dominant
Genes, Reporter
Green Fluorescent Proteins / metabolism
Luciferases / metabolism
Models, Genetic
Mutation
Oligonucleotides, Antisense / chemistry
Promoter Regions, Genetic
Protein Binding
Proto-Oncogene Proteins c-jun / metabolism*
Rats
Time Factors
Transfection
Chemical
Reg. No./Substance:
0/Ccna2 protein, rat; 0/Cyclin A; 0/Cyclin A2; 0/Oligonucleotides, Antisense; 0/Proto-Oncogene Proteins c-jun; 147336-22-9/Green Fluorescent Proteins; 564-25-0/Doxycycline; EC 1.13.12.-/Luciferases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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