EWS/Fli-1 chimeric protein is a transcriptional activator.

Abstract

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.

• Authors: T Ohno, V N Rao, E S Reddy
• Journal: Cancer research (Cancer Res) Vol. 53 Issue 24 Pg. 5859-63 (Dec 15 1993) ISSN: 0008-5472 [Print] United States
• PMID: 7503813 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• 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

Topics

• 3T3 Cells
• Animals
• DNA, Complementary (isolation & purification)
• DNA-Binding Proteins (genetics, 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, physiology)