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  • Original Paper
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EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function

Oncogene volume 20, pages 6653–6659 (2001)Cite this article

Abstract

The recurrent t(12;22) (q13;q12) chromosomal translocation associated with soft tissue clear cell sarcoma results in a chimeric protein EWS-ATF-1 that acts as a constitutive transcriptional activator. The CBP/p300 transcriptional coactivator, which links various transcriptional factors to basal transcription apparatus, participates in transcriptional activation, growth and cell cycle control and differentiation. In this study, we show that EWS-ATF-1 associates constitutively with CBP both in vitro and in vivo. Both EWS and ATF-1 fusion domains are needed for this interaction. Here, we demonstrate that EWS-ATF-1 represses p53/CBP-mediated trans-activation function. Overexpression of CBP can counteract this repressive effect of EWS-ATF-1. Taken together, these findings suggest that one of the mechanisms by which EWS-ATF-1 may cause tumors is through targeting CBP/p300 resulting in the loss of function of p53. This novel mechanism may be responsible for the development of these and other related solid tumors.

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Acknowledgements

We thank other colleagues of Reddy and Rao's laboratories for their kind cooperation. This work is supported in part by NIH grants RO1 CA 85343, RO1 CA 58642 and US Army medical research and command grant DAMD-17-99-1-9060 to ESP Reddy and CA 57322 to VN Rao.

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Authors and Affiliations

  1. Department of Biochemistry, Program of Cancer Genetics, Cancer center, MS #481, School of Medicine, MCP Hahnemann University, Broad and Vine, Philadelphia, PA 19102, Pennsylvania, USA

    Yasuo Fujimura, Habibur Siddique, Veena N Rao & E Shyam P Reddy

  2. SAIC, Frederick, MD 21702, Maryland, USA

    Leo Lee

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  1. Yasuo Fujimura
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  2. Habibur Siddique
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Fujimura, Y., Siddique, H., Lee, L. et al. EWS-ATF-1 chimeric protein in soft tissue clear cell sarcoma associates with CREB-binding protein and interferes with p53-mediated trans-activation function. Oncogene 20, 6653–6659 (2001). https://doi.org/10.1038/sj.onc.1204684

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