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  • Original Paper
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Human Dbf4/ASK promoter is activated through the Sp1 and MluI cell-cycle box (MCB) transcription elements

Oncogene volume 21, pages 7786–7796 (2002)Cite this article

Abstract

Dbf4 is the regulatory subunit of Cdc7 kinase, which is essential for entry into and traversing through S phase. The level of Dbf4, which is critical for the activation of Cdc7, is regulated by transcription and protein degradation. To gain a better understanding as to how the transcription of human Dbf4 (HuDbf4) is regulated, we have cloned and characterized its promoter. We found that HuDbf4 core promoter is localized within −211 to −285 of the translation start-codon. This 75 bp DNA segment contains, among others, a putative MluI Cell-cycle Box (MCB). A point mutation within the MCB dramatically reduced the promoter activity. This is the first example that an MCB element plays an essential role in the activation of a core promoter in mammalian cells. The auxiliary elements required for the full promoter activity are present within 162-bp upstream from the core promoter (i.e., −286/−447). A point mutation within the Sp1 element at −353/−361 resulted in a decrease of promoter activity to the basal level, while the deletion of the putative HES-1 at −326/−331 dramatically increased the promoter activity. Taken together, our data suggests that the MCB element is essential for the core promoter activation, while the Sp1 positive regulator and the HES-1 repressor coordinately determine the efficiency of the HuDbf4 promoter. We have also found: (i) that the major transcription initiations occur at −220, −235 and −245; (ii) that HuDbf4 gene consists of 12 exons, which spread over a 33-kb region.

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Acknowledgements

We thank the members of the Lee lab, particularly, B Guo and A Pearce for many helpful discussions. This work was supported by the operating grants from the Canadian Institutes of Health Research (MT-15015), Northern Cancer Research Foundation, and the Northern Ontario Heritage Fund Corporation (NOHFC #50070). H Lee is a recipient of the Premier's Research Excellence Award.

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  1. Northeastern Ontario Regional Cancer Centre, Sudbury, Ontario, P3E 5J1, Canada

    Xing Wu & Hoyun Lee

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Correspondence to Hoyun Lee.

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Wu, X., Lee, H. Human Dbf4/ASK promoter is activated through the Sp1 and MluI cell-cycle box (MCB) transcription elements. Oncogene 21, 7786–7796 (2002). https://doi.org/10.1038/sj.onc.1205914

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