EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction

Oncogene. 1998 Oct 22;17(16):2039-45. doi: 10.1038/sj.onc.1202129.


The EWS/FLI1 fusion gene found in Ewing's sarcoma and primitive neuroectodermal tumor, is able to transform certain cell lines by acting as an aberrant transcription factor. The ability of EWS/FLI1 to modulate gene expression in cells transformed and resistant to transformation by EWS/FLI1, was assessed by Representational Difference Analysis (RDA). We found that the cyclin selective ubiquitin conjugase murine E2-C, was up regulated in NIH3T3 cells transformed by EWS/FLI1 but not in a nontransformed NIH3T3 clone expressing EWS/FLI1. We also found that mE2-C is upregulated in NIH3T3 cells transformed by other genes including activated cdc42, v-ABL and c-myc. We demonstrated that expression of mE2-C in both the EWS/FLI1 transformed and parent NIH3T3 lines varies with the cell cycle. Finally, dominant-negative mE2-C, created by changing a catalytic cysteine to serine, inhibits the in vitro ubiquitination and degradation of cyclin B in human HeLa cell extracts. These data suggest that part of the biologic effect of EWS/FLI1 could be to transcriptionally modulate genes involved in cell cycle regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / biosynthesis*
  • Cell Cycle
  • Cell Line, Transformed
  • Cell Transformation, Neoplastic
  • Cell-Free System
  • Cyclin B / metabolism*
  • Gene Expression
  • Humans
  • Ligases*
  • Mice
  • Molecular Sequence Data
  • Oncogene Proteins, Fusion / genetics
  • Oncogene Proteins, Fusion / metabolism*
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitin-Conjugating Enzymes*
  • Up-Regulation*


  • Carrier Proteins
  • Cyclin B
  • EWS-FLI fusion protein
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • Transcription Factors
  • ubiquitin carrier proteins
  • Ubiquitin-Conjugating Enzymes
  • Ligases