The oncoprotein DEK controls growth-regulated gene expression by enhancing the DNA-binding activity of basic leucine zipper transcription factors.

Abstract

Overexpression of the oncogenic protein DEK is associated with a poor prognosis in various cancers. However, the molecular mechanisms by which DEK promotes cancer development and malignant transformation remain unclear. Previous studies have shown that DEK interacts with transcription factors, such as AP-2a and C/EBPα, and enhances their transcriptional activity. We hypothesized that DEK promotes cancer cell phenotypes by regulating transcription factors. We analyzed the interaction between DEK and the transcription factors to evaluate this hypothesis. We found that DEK binds to the basic regions within the basic leucine zipper (bZIP)- and basic helix-loop-helix leucine zipper (bHLH-ZIP)- transcription factors. Interestingly, DEK enhanced the DNA-binding capacity of two bZIP transcription factors, C/EBPα and ATF3, in vitro without being a component of the transcription factor-DNA complex. We performed DEK knockdown in lung adenocarcinoma A549 cells and examined the global transcriptome changes to determine the biological significance of the interaction between DEK and transcription factors. We found that diverse genes regulating cell growth and amino acid metabolism, which may potentially be regulated by c-Jun, a subunit of the bZIP transcription factor AP1, and c-Myc, a bHLH-ZIP transcription factor, were decreased by DEK knockdown. Consistent with these transcriptome changes, the cell growth, colony formation, and cell migration abilities of A549 cells were decreased by DEK knockdown. These results suggest that DEK promotes cancer cell malignancy by regulating the functions of the bZIP and bHLH-ZIP transcription factors.