title: The PAX3-FOXO1 fusion protein present in rhabdomyosarcoma interferes with normal FOXO activity and the TGF-β pathway.
abstract: PAX3-FOXO1 (PAX3-FKHR) is the fusion protein produced by the genomic translocation that characterizes the alveolar subtype of Rhabdomyosarcoma, a pediatric sarcoma with myogenic phenotype. PAX3-FOXO1 is an aberrant but functional transcription factor. It retains PAX3-DNA-binding activity and functionally overlaps PAX3 function while also disturbing it, in particular its role in myogenic differentiation. We herein show that PAX3-FOXO1 interferes with normal FOXO function. PAX3-FOXO1 affects FOXO-family member trans-activation capability and the FOXO-dependent TGF-β response. PAX3-FOXO1 may contribute to tumor formation by inhibiting the tumor suppressor activities which are characteristic of both FOXO family members and TGF-β pathways. The recognition of this mechanism raises new questions about how FOXO family members function.
authors: Molecular Biotechnology Center and Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Michel
authors: M
authors: Schmitt-Ney
authors: Molecular Biotechnology Center and Department of Medical Sciences, University of Torino, Torino, Italy.
authors: Giovanni
authors: G
authors: Camussi
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D012208:Rhabdomyosarcoma / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D015514:Oncogene Proteins, Fusion; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; C471563:PAX3-FOXO1A fusion protein, human; D051761:Paired Box Transcription Factors; D016212:Transforming Growth Factor beta