Guilt by association: PAX3-FOXO1 regulates gene expression through selective destabilization of the EGR1 transcription factor.

Abstract

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.

• Authors: Wendy Roeb, Antonia Boyer, Webster K Cavenee, Karen C Arden
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 7 Issue 7 Pg. 837-41 (Apr 01 2008) ISSN: 1551-4005 [Electronic] United States
• PMID: 18414034 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Early Growth Response Protein 1
• FOXO1 protein, human
• Forkhead Box Protein O1
• Forkhead Transcription Factors
• PAX3 Transcription Factor
• PAX3 protein, human
• Paired Box Transcription Factors

Topics

• Blotting, Western
• Cell Differentiation (physiology)
• Cell Line
• Early Growth Response Protein 1 (metabolism)
• Forkhead Box Protein O1
• Forkhead Transcription Factors (metabolism)
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Immunoprecipitation
• Models, Biological
• Myoblasts (cytology)
• PAX3 Transcription Factor
• Paired Box Transcription Factors (metabolism)
• Rhabdomyosarcoma, Alveolar (metabolism)
• Ubiquitination