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

Afsane Arvand, Holger Bastians, Scott Welford, Andrew D. Thompson, Joan V. Ruderman, Christopher T. Denny

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2039-2045
Number of pages7
JournalOncogene
Volume17
Issue number16
DOIs
StatePublished - Oct 22 1998
Externally publishedYes

Fingerprint

Cyclin C
Ubiquitin-Conjugating Enzymes
Cyclin B
Up-Regulation
Cell Cycle
gamma-Glutamyl Hydrolase
Primitive Neuroectodermal Tumors
Ewing's Sarcoma
Cyclins
Gene Fusion
Ubiquitination
Ubiquitin
EWS-FLI fusion protein
Cell Extracts
HeLa Cells
Serine
Genes
Cysteine
Transcription Factors
Clone Cells

Keywords

  • Cell cycle
  • E2-C
  • Ewing's sarcoma
  • EWS/FLI1
  • RDA
  • Transformation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction. / Arvand, Afsane; Bastians, Holger; Welford, Scott; Thompson, Andrew D.; Ruderman, Joan V.; Denny, Christopher T.

In: Oncogene, Vol. 17, No. 16, 22.10.1998, p. 2039-2045.

Research output: Contribution to journalArticle

Arvand, Afsane ; Bastians, Holger ; Welford, Scott ; Thompson, Andrew D. ; Ruderman, Joan V. ; Denny, Christopher T. / EWS/FLI1 up regulates mE2-C, a cyclin-selective ubiquitin conjugating enzyme involved in cyclin B destruction. In: Oncogene. 1998 ; Vol. 17, No. 16. pp. 2039-2045.
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