Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Cyclin A is a c-Jun target gene and is necessary for c-Jun-induced anchorage-independent growth in RAT1a cells. 1573 94