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EWS/Fli-1 chimeric protein is a transcriptional activator.
Cancer Res. 1993 Dec 15; 53(24):5859-63.CR

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+Show Affiliations

Department of Microbiology and Immunology, Jefferson Cancer Institute, Philadelphia, Pennsylvania 19107-5541.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

7503813

Citation

Ohno, T, et al. "EWS/Fli-1 Chimeric Protein Is a Transcriptional Activator." Cancer Research, vol. 53, no. 24, 1993, pp. 5859-63.
Ohno T, Rao VN, Reddy ES. EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Res. 1993;53(24):5859-63.
Ohno, T., Rao, V. N., & Reddy, E. S. (1993). EWS/Fli-1 chimeric protein is a transcriptional activator. Cancer Research, 53(24), 5859-63.
Ohno T, Rao VN, Reddy ES. EWS/Fli-1 Chimeric Protein Is a Transcriptional Activator. Cancer Res. 1993 Dec 15;53(24):5859-63. PubMed PMID: 7503813.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - EWS/Fli-1 chimeric protein is a transcriptional activator. AU - Ohno,T, AU - Rao,V N, AU - Reddy,E S, PY - 1993/12/15/pubmed PY - 1993/12/15/medline PY - 1993/12/15/entrez SP - 5859 EP - 63 JF - Cancer research JO - Cancer Res VL - 53 IS - 24 N2 - 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/7503813/EWS/Fli_1_chimeric_protein_is_a_transcriptional_activator_ DB - PRIME DP - Unbound Medicine ER -