Promoters containing ATF-binding sites are de-regulated in cells that express the EWS/ATF1 oncogene

Oncogene. 1995 May 4;10(9):1749-56.


Chromosomal translocations that fuse the N-terminal region of the Ewings sarcoma oncogene (EWS) to the C-terminal region (including the DNA-binding domain) of the cellular transcription factor ATF1 are associated with a tumour type termed malignant melanoma of soft parts (MMSP). It is envisioned that transformation by the EWS/ATF1 fusion protein results from aberrant transcriptional regulation of genes that are normally regulated by ATF1. To examine this hypothesis we have expressed exogenous EWS-ATF1 in JEG3 cells and tested its ability to activate several promoters that contain binding sites for ATF1. We show that EWS-ATF1 is a strong constitutive activator of some promoters tested but represses others. Significantly, the ability of particular promoters to be activated by EWS/ATF1 in JEG3 cells correlates with promoter activity in two MMSP-derived cell lines (SU-CCS-1 and DTC1). Our results therefore provide evidence that endogenous EWS/ATF1 can de-regulate transcription and that this capacity may contribute to transformation in MMSP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activating Transcription Factor 1
  • Base Sequence
  • Chromosome Aberrations / genetics
  • Chromosome Disorders
  • DNA-Binding Proteins / genetics
  • Gene Expression Regulation*
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • In Vitro Techniques
  • Melanoma / genetics*
  • Molecular Sequence Data
  • Nuclear Proteins / genetics*
  • Oligodeoxyribonucleotides / chemistry
  • Promoter Regions, Genetic*
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / genetics*
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Ribonucleoproteins / genetics*
  • Transcription Factors / genetics*
  • Transcription, Genetic
  • Translocation, Genetic


  • Activating Transcription Factor 1
  • DNA-Binding Proteins
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nuclear Proteins
  • Oligodeoxyribonucleotides
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Recombinant Proteins
  • Ribonucleoproteins
  • Transcription Factors