Transcriptional co-factor CDCA4 participates in the regulation of JUN oncogene expression

Biochimie. 2008 Oct;90(10):1515-22. doi: 10.1016/j.biochi.2008.05.014. Epub 2008 Jun 3.

Abstract

CDCA4, a member of the TRIP-Br transcriptional co-factor family, has been shown to possess a unique role in regulating the transcriptional activities of p53 as well as E2F1 transcription factors. In this study, we aimed to identify a pivotal transcriptional target gene regulated by CDCA4, so we suppressed CDCA4 expression by CDCA4-specific short interference RNA (siRNA) in HeLa cells, and then performed a DNA microarray analysis. Among the identified genes, we focused on JUN, 14-3-3eta, and IL6ST (gp130) mRNAs which were up-regulated in CDCA4-specific siRNA-transfected cells compared to control siRNA-transfected cells. We confirmed that JUN, 14-3-3eta, and IL6ST proteins were up-regulated when cells were transfected with CDCA4-specific siRNA. 14-3-3eta and IL6ST protein levels were unchanged upon on transfection of cells with JUN-specific siRNA, indicating that 14-3-3eta and IL6ST genes are not a direct target of JUN. Serine 63 and 73 phosphorylation of JUN was unchanged when cells were transfected with CDCA4-specific siRNA. In addition, JUN-driven reporter activity was unaffected by CDCA4 co-transfection, suggesting that CDCA4 affects solely JUN mRNA expression. Finally, by preparing various JUN promoter reporter constructs, we minimized the JUN promoter sequence that was affected by CDCA4 co-expression. Together, these results add an important role of CDCA4 in the context of transcriptional regulation and cell fate determination through the JUN oncogene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • E2F1 Transcription Factor / metabolism
  • GC Rich Sequence
  • Gene Expression Regulation*
  • Genes, jun / genetics*
  • HeLa Cells
  • Humans
  • Luciferases / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Promoter Regions, Genetic / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • CDCA4 protein, human
  • Cell Cycle Proteins
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Tumor Suppressor Protein p53
  • Luciferases