Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1

Exp Dermatol. 2008 Dec;17(12):986-91. doi: 10.1111/j.1600-0625.2008.00730.x. Epub 2008 May 21.


Background: Melanoma is a complex genetic disease, the management of which will require an in-depth understanding of the biology underlying its initiation and progression. Recently, we have reported the differential regulation of a novel gene, namely ASK/Dbf4, in melanoma and suggested upregulation of ASK/Dbf4 as a novel molecular determinant with prognostic relevance that confers a proliferative advantage in cutaneous melanoma. As trans-acting factor binding is fundamental to understand the regulation of gene expression, this study focuses on characterization of the specific transcriptional regulation of ASK/Dbf4 in melanoma.

Objective: We investigated whether ASK/Dbf4 is a transcriptional target of the important cell cycle regulator E2F1 in melanoma.

Results: As evidenced by gel supershift assays on nuclear extracts from various melanoma cell lines (SK-MEL-28, MV3, M13, A375 and BLM), E2F1 bound to the ASK/Dbf4 minimal promoter (MP). In addition, cisplatin-mediated abrogation of E2F1 binding to the ASK/Dbf4 MP resulted in a transcriptional decrease in ASK/Dbf4. Further, the current study also demonstrated that ASK/Dbf4 regulation was refractory to UVB, a well-known risk factor for melanoma.

Conclusions: In summary, our study not only elucidated that ASK/Dbf4, a novel cell survival gene in melanoma was transcriptionally regulated by E2F1, but also that the induction of ASK/Dbf4 was refractory to UVB exposure suggesting that its upregulation was not an early event in melanomagenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Electrophoretic Mobility Shift Assay
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Melanocytes / drug effects
  • Melanocytes / metabolism
  • Melanocytes / radiation effects
  • Melanoma / genetics
  • Melanoma / metabolism
  • Melanoma / pathology*
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • Protein Binding / radiation effects
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Ultraviolet Rays


  • Antineoplastic Agents
  • Cell Cycle Proteins
  • DBF4 protein, human
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Tumor Suppressor Protein p53
  • Cisplatin