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Role of protein-protein interactions in the antiapoptotic function of EWS-Fli-1

  1. Author:
    Ramakrishnan, R.
    Fujimura, Y.
    Zou, J. P.
    Liu, F.
    Lee, L.
    Rao, V. N.
    Reddy, E. S. P.

  2. Author Address

    Georgia Canc Ctr Excellence, Morehouse Sch Med, Dept Med, Canc Biol Program, Atlanta, GA 30303 USA. Drexel Univ, Philadelphia, PA 19102 USA. SAIC, Frederick, MD 21702 USA Reddy, ESP, Georgia Canc Ctr Excellence, Morehouse Sch Med, Dept Med, Canc Biol Program, 80 Jessie Hill Jr Dr, Atlanta, GA 30303 USA
    1. Year: 2004
    2. Date: SEP 16
  2. Journal: Oncogene
    1. 23
    2. 42
    3. Pages: 7087-7094
  4. Type of Article: Article
  1. Abstract:

    In the majority of Ewing's family tumors, chromosomal translocation t(11; 22) leads to aberrant fusion of RNA-binding protein EWS with DNA-binding ETS transcriptional factor Fli-1. EWS-Fli-1 has altered the transcriptional activity and modulating its downstream target genes through this transcriptional activity is thought to be responsible for this tumor. We have previously shown that both EWS-Fli-1 and Fli-1 have antiapoptotic activity against several apoptotic inducers. Here, we show that the transcriptional activity of EWS-Fli-1 and Fli-1 is not essential for its antiapoptotic activity. We also demonstrate that EWS-Fli-1 and Fli-1 interact with CBP through its amino-terminal region and inhibit the CBP-dependent transcriptional activity of RXR. This activity appears to be independent of DNA-binding activity of EWS-Fli-1. Introduction of the dominant-negative form of CBP into Ewing's sarcoma cells sensitizes these cells against genotoxic or retinoic-acid induced apoptosis. These results suggest that the ability of EWS-Fli-1/Fli-1 to target transcriptional cofactor(s) and modulate apoptotic pathways may be responsible for its antiapoptotic and tumorigenic activities

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External Sources

  1. View record in Web of Science®
  2. WOS: 000223885100009

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