Differential requirement for dimerization partner DP between E2F-dependent activation of tumor suppressor and growth-related genes

Sci Rep. 2018 May 31;8(1):8438. doi: 10.1038/s41598-018-26860-0.


The transcription factor E2F plays crucial roles in cell proliferation and tumor suppression by activating growth-related genes and pro-apoptotic tumor suppressor genes, respectively. It is generally accepted that E2F binds to target sequences with its heterodimeric partner DP. Here we show that, while knockdown of DP1 expression inhibited ectopic E2F1- or adenovirus E1a-induced expression of the CDC6 gene and cell proliferation, knockdown of DP1 and DP2 expression did not affect ectopic E2F1- or E1a-induced expression of the tumor suppressor ARF gene, an upstream activator of the tumor suppressor p53, activation of p53 or apoptosis. These observations suggest that growth related and pro-apoptotic E2F targets are regulated by distinct molecular mechanisms and contradict the threshold model, which postulates that E2F activation of pro-apoptotic genes requires a higher total activity of activator E2Fs, above that necessary for E2F-dependent activation of growth-related genes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism
  • Apoptosis
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line
  • DNA-Binding Proteins / antagonists & inhibitors
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • E2F1 Transcription Factor / chemistry
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Humans
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Transcription Factor DP1 / antagonists & inhibitors
  • Transcription Factor DP1 / genetics
  • Transcription Factor DP1 / metabolism*
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Tumor Suppressor Protein p53 / metabolism*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F1 Transcription Factor
  • RNA, Small Interfering
  • TFDP2 protein, human
  • TP53 protein, human
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • ADP-Ribosylation Factors