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http://purl.uniprot.org/citations/12543801http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12543801http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12543801http://www.w3.org/2000/01/rdf-schema#comment"Nuclear receptors represent a large family of transcription factors involved in development, differentiation, homeostasis, and cancer. In recent years, a growing number of cofactors has been discovered that participate in the regulation of the transcriptional activity of these proteins. We present in this study the identification of a cofactor, the homeotic protein Six3, which differentially regulates the transcriptional activity of the orphan nuclear receptor NOR-1 (NR4A3). NOR-1 is normally involved in the balance between cell proliferation and cell death, and is implicated in oncogenesis as part of the EWS/NOR-1 fusion protein found in human extraskeletal myxoid chondrosarcoma (EMC) tumors. Reverse transcription-PCR analyses indicate that EMC tumors expressing the EWS/NOR-1 mRNA also express mRNAs encoding NOR-1 and Six3. Glutathione S-transferase fusion protein assays show that Six3 binds in vitro the DNA-binding domain of NOR-1 and the EWS domain of EWS/NOR-1 and that the homeodomain of Six3 is required for these interactions. Mammalian two-hybrid experiments, using immortalized human chondrocytes as a model, indicate that Six3 also interacts with NOR-1 and EWS/NOR-1 in vivo. Cotransfection experiments show that Six3 stimulates the transcriptional activity of NOR-1, whereas it represses that of EWS/NOR-1. Considering the highly specific expression pattern of Six3, our finding that it is expressed in EMC suggests that it plays a pivotal role in the development of these tumors. We propose that Six3 maintains a transcriptional balance between the activities of NOR-1 and EWS/NOR-1, the net effect being to deregulate the expression of specific target genes and push the equilibrium toward uncontrolled cell proliferation."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Ladanyi M."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Ladanyi M."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Goldring M.B."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Goldring M.B."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Bridge J.A."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Bridge J.A."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Labelle Y."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Labelle Y."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Laflamme C."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Laflamme C."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Filion C."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/author"Filion C."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/name"Cancer Res."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/name"Cancer Res."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/pages"449-454"xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/pages"449-454"xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/title"The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/title"The homeotic protein Six3 is a coactivator of the nuclear receptor NOR-1 and a corepressor of the fusion protein EWS/NOR-1 in human extraskeletal myxoid chondrosarcomas."xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/volume"63"xsd:string
http://purl.uniprot.org/citations/12543801http://purl.uniprot.org/core/volume"63"xsd:string
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