EWS/Fli-1 chimeric protein is a transcriptional activator

Cancer Res. 1993 Dec 15;53(24):5859-63.


Fli-1, an ets related gene, was found to be rearranged in 75% of erythroleukemias induced by Friend murine leukemia virus. We have shown previously that the Fli-1 gene codes for a sequence specific transcriptional activator which contains two autonomous transcriptional activation domains, one at the amino terminal region and the other at the carboxy terminal region. Recently human Fli-1 gene was shown to be involved in Ewing's sarcoma and related subtypes of primitive neuroectodermal tumors which share t(11;22) (q24;q12) chromosome translocation. In these tumors the carboxyl terminal region of Fli-1 was found to be fused with the amino terminal region of a putative RNA binding protein, EWS. Because part of the amino terminal transcriptional activation domain of Fli-1 was replaced with the amino terminal domain of the EWS (NTD-EWS) which shares homology with RNA polymerase II, it was speculated that NTD-EWS may interfere with RNA pol II function. Alternatively, NTD-EWS could also contribute to the transcriptional activation function of EWS/Fli-1 chimeric protein by providing either a modulatory/regulatory domain or a novel transcriptional activation domain. Here we show that EWS/Fli-1 chimeric protein functions as a transcriptional activator. Deletion analysis reveals that the EWS domain functions as a modulatory/regulatory domain for the transcriptional activation properties of the carboxy terminal transcriptional activation domain of EWS/Fli-1. We therefore propose that replacement of the amino terminal transcriptional activation domain of the Fli-1 protein with the regulatory domain of NTD-EWS results in the activation of the carboxy terminal transcriptional activation domain of Fli-1 which may be the molecular mechanism involved in these human tumors.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • DNA, Complementary / isolation & purification
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Mice
  • Nuclear Proteins / physiology
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins*
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins / physiology*
  • Recombinant Fusion Proteins / physiology*
  • Ribonucleoproteins / physiology*
  • Sarcoma, Ewing / genetics*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • DNA, Complementary
  • DNA-Binding Proteins
  • Fli1 protein, mouse
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Nuclear Proteins
  • Proto-Oncogene Protein c-fli-1
  • Proto-Oncogene Proteins
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • Ribonucleoproteins
  • Trans-Activators