A genetic analysis of PAX3-FKHR, the oncogene of alveolar rhabdomyosarcoma.

Abstract

The PAX3-FKHR fusion protein of human alveolar rhabdomyosarcoma consists of the DNA-binding domains of PAX3 and the transcriptional activation domain of FKHR. It induces oncogenic transformation in cultures of chicken embryo fibroblasts (CEFs). PAX3-FKHR-transformed CEFs have been kept in continuous culture for more than 1 year; when quiescent, portions of the cultures differentiate into several distinct cell types. Deletion analysis suggests that both DNA binding and transcriptional activation are required for the induction of the PAX3-FKHR-transformed cellular phenotype. Mutant PAX3-FKHR proteins with reduced DNA binding or transactivation induce altered cellular morphologies and growth behavior distinct from that of CEFs expressing wild-type PAX3-FKHR. Mutant proteins that completely lack DNA binding or transactivation potential fail to transform.

• Authors: B E Kempf, P K Vogt
• Journal: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research (Cell Growth Differ) Vol. 10 Issue 12 Pg. 813-8 (Dec 1999) ISSN: 1044-9523 [Print] United States
• PMID: 10616906 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• DNA-Binding Proteins
• FOXO1 protein, human
• Forkhead Box Protein O1
• Forkhead Transcription Factors
• Oncogene Proteins
• PAX3 Transcription Factor
• PAX3 protein, human
• Paired Box Transcription Factors
• Recombinant Fusion Proteins
• Transcription Factors
• Pax3 protein, mouse
• DNA

Topics

• Animals
• Cell Transformation, Neoplastic
• Chick Embryo
• DNA (metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Fibroblasts (cytology)
• Forkhead Box Protein O1
• Forkhead Transcription Factors
• Humans
• Mutagenesis
• Oncogene Proteins (genetics, metabolism)
• PAX3 Transcription Factor
• Paired Box Transcription Factors
• Recombinant Fusion Proteins (genetics, metabolism)
• Rhabdomyosarcoma, Alveolar (genetics)
• Sequence Deletion
• Transcription Factors (genetics, metabolism)
• Transcriptional Activation