title: 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.affiliation: The Scripps Research Institute, Division of Molecular and Experimental Medicine, La Jolla, California 92037, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Kempf
authors.forename: P K
authors.initials: PK
authors.lastname: Vogt
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006801:Humans; D016296:Mutagenesis; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D018232:Rhabdomyosarcoma, Alveolar / Q000235:genetics*; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D004268:DNA-Binding Proteins; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015513:Oncogene Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C068686:Pax3 protein, mouse; D004247:DNA