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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Transformation, Neoplastic*
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Chick Embryo
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DNA / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Fibroblasts / cytology
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Humans
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Mutagenesis
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Oncogene Proteins / genetics
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Oncogene Proteins / metabolism*
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PAX3 Transcription Factor
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Paired Box Transcription Factors
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Rhabdomyosarcoma, Alveolar / genetics*
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Sequence Deletion
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
Substances
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DNA-Binding Proteins
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FOXO1 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Oncogene Proteins
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PAX3 Transcription Factor
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PAX3 protein, human
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Paired Box Transcription Factors
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Recombinant Fusion Proteins
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Transcription Factors
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Pax3 protein, mouse
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DNA