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Mol Cell Biol, July 1998, p. 4118-4130, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Tumor-Specific PAX3-FKHR Transcription Factor, but Not PAX3, Activates the Platelet-Derived Growth Factor Alpha Receptor

Jonathan A. Epstein,1 Baoliang Song,2 Maha Lakkis,1 and Chiayeng Wang2 *

Cardiovascular Division, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104,1 and Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, Chicago, Illinois 606122

Received 20 October 1997/Returned for modification 15 December 1997/Accepted 6 April 1998

The t(2;13) chromosomal translocation occurs at a high frequency in alveolar rhabdomyosarcoma, a common pediatric tumor of muscle. This translocation results in the production of a chimeric fusion protein derived from two developmentally regulated transcription factors, PAX3 and FKHR. The two DNA binding modules, the paired domain and the homeodomain, of PAX3 are fused in frame to the transactivation domain of FKHR. Previously, tumor-specific PAX3-FKHR has been shown to bind to DNA sequences normally recognized by wild-type PAX3 and to exhibit relatively enhanced transcriptional activity. The DNA binding sites used to demonstrate that PAX3-FKHR is a more potent transcriptional activator than PAX3 have included recognition sequences for the paired domain of PAX3. In this report, we demonstrate the ability of PAX3-FKHR to activate the product of a growth control gene, platelet-derived growth factor alpha receptor (PDGFalpha R), by recognizing a paired-type homeodomain binding site located in the PDGFalpha R promoter. PAX3 alone cannot mediate transcriptional activation of this promoter under the conditions tested. This provides the first evidence that chromosomal translocation results in altered target gene specificity of PAX3-FKHR and suggests a transcriptional target that may play a significant role in oncogenic activity and rhabdomyosarcoma development.

* Corresponding author. Mailing address: Center for Molecular Biology of Oral Diseases, University of Illinois at Chicago, 801 South Paulina St., Chicago, IL 60612. Phone: (312) 996-4530. Fax: (312) 413-1604. E-mail: U30080{at}uicvm.cc.uic.edu.

Mol Cell Biol, July 1998, p. 4118-4130, Vol. 18, No. 7
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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