The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1

William A. May, Stephen L. Lessnick, Benjamin S. Braun, Michael Klemsz, Brian C. Lewis, Lynn B. Lunsford, Robert Hromas, Christopher T. Denny

Research output: Contribution to journalArticle

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Abstract

EWS/FLI-1 is a chimeric protein formed by a tumor-specific 11;22 translocation found in both Ewing's sarcoma and primitive neuroectodermal tumor of childhood. EWS/FLI-1 has been shown to be a potent transforming gene, suggesting that it plays an important role in the genesis of these human tumors. We now demonstrate that EWS/FLI-1 has the characteristics of an aberrant transcription factor. Subcellular fractionation experiments localized the EWS/FLI-1 protein to the nucleus of primitive neuroectodermal tumor cells. EWS/FLI-1 specifically bound in vitro an ets-2 consensus sequence similarly to normal FLI-1. When coupled to a GAL4 DNA-binding domain, the amino-terminal EWS/FLI-1 region was a much more potent transcriptional activator than the corresponding amino-terminal domain of FLI-1. Finally, EWS/FLI-1 efficiently transformed NIH 3T3 cells, but FLI-1 did not. These data suggest that EWS/FLI-1, functioning as a transcription factor, leads to a phenotype dramatically different from that of cells expressing FLI-1. EWS/FLI-1 could disrupt normal growth and differentiation either by more efficiently activating FLI-1 target genes or by inappropriately modulating genes normally not responsive to FLI-1.

Original languageEnglish
Pages (from-to)7393-7398
Number of pages6
JournalMolecular and Cellular Biology
Volume13
Issue number12
StatePublished - Dec 1993
Externally publishedYes

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Ewing's Sarcoma
Gene Fusion
Oncogenes
Primitive Neuroectodermal Tumors
Transcription Factors
EWS-FLI fusion protein
NIH 3T3 Cells
Consensus Sequence
Genes
Neoplasms
Proteins
Phenotype
DNA

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

Cite this

May, W. A., Lessnick, S. L., Braun, B. S., Klemsz, M., Lewis, B. C., Lunsford, L. B., ... Denny, C. T. (1993). The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Molecular and Cellular Biology, 13(12), 7393-7398.

The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. / May, William A.; Lessnick, Stephen L.; Braun, Benjamin S.; Klemsz, Michael; Lewis, Brian C.; Lunsford, Lynn B.; Hromas, Robert; Denny, Christopher T.

In: Molecular and Cellular Biology, Vol. 13, No. 12, 12.1993, p. 7393-7398.

Research output: Contribution to journalArticle

May, WA, Lessnick, SL, Braun, BS, Klemsz, M, Lewis, BC, Lunsford, LB, Hromas, R & Denny, CT 1993, 'The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1', Molecular and Cellular Biology, vol. 13, no. 12, pp. 7393-7398.
May, William A. ; Lessnick, Stephen L. ; Braun, Benjamin S. ; Klemsz, Michael ; Lewis, Brian C. ; Lunsford, Lynn B. ; Hromas, Robert ; Denny, Christopher T. / The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. In: Molecular and Cellular Biology. 1993 ; Vol. 13, No. 12. pp. 7393-7398.
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