Guilt by association: PAX3-FOXO1 regulates gene expression through selective destabilization of the EGR1 transcription factor
Copyright policy )Guilt by association: PAX3-FOXO1 regulates gene expression through selective destabilization of the EGR1 transcription factor
Human cancer cells frequently harbor chromosomal translocations that create chimeric fusion genes. The t(2;13) translocation is characteristic of the pediatric muscle tumor, alveolar rhabdomyosarcoma, and produces the chimeric transcription factor, PAX3-FOXO1, that contains the DNA binding elements of PAX3 and the transcriptional activation domain of FOXO1. Experiments designed to determine how PAX3-FOXO1 expression contributes to the development of muscle cell-derived tumors resulted in the discovery that the fusion protein misregulates gene expression and interrupts myogenic differentiation through a unique gain of function mechanism. These results yield new insight into how tumor-associated genetic alterations increase the likelihood of cancer formation and may lead to new therapeutic approaches.
- Ludwig Cancer Research United States
- University of California, San Diego United States
Forkhead Box Protein O1, Blotting, Western, Ubiquitination, Cell Differentiation, Forkhead Transcription Factors, Models, Biological, Cell Line, Gene Expression Regulation, Neoplastic, Myoblasts, Humans, Immunoprecipitation, Paired Box Transcription Factors, PAX3 Transcription Factor, Rhabdomyosarcoma, Alveolar, Early Growth Response Protein 1
Forkhead Box Protein O1, Blotting, Western, Ubiquitination, Cell Differentiation, Forkhead Transcription Factors, Models, Biological, Cell Line, Gene Expression Regulation, Neoplastic, Myoblasts, Humans, Immunoprecipitation, Paired Box Transcription Factors, PAX3 Transcription Factor, Rhabdomyosarcoma, Alveolar, Early Growth Response Protein 1
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