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The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway

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 functio...

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Detalles Bibliográficos
Autores principales: Schmitt-Ney, Michel, Camussi, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373809/
https://www.ncbi.nlm.nih.gov/pubmed/25806826
http://dx.doi.org/10.1371/journal.pone.0121474
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author Schmitt-Ney, Michel
Camussi, Giovanni
author_facet Schmitt-Ney, Michel
Camussi, Giovanni
author_sort Schmitt-Ney, Michel
collection PubMed
description 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.
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spelling pubmed-43738092015-03-27 The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway Schmitt-Ney, Michel Camussi, Giovanni PLoS One Research Article 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. Public Library of Science 2015-03-25 /pmc/articles/PMC4373809/ /pubmed/25806826 http://dx.doi.org/10.1371/journal.pone.0121474 Text en © 2015 Schmitt-Ney, Camussi http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Schmitt-Ney, Michel
Camussi, Giovanni
The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway
title The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway
title_full The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway
title_fullStr The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway
title_full_unstemmed The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway
title_short The PAX3-FOXO1 Fusion Protein Present in Rhabdomyosarcoma Interferes with Normal FOXO Activity and the TGF-β Pathway
title_sort pax3-foxo1 fusion protein present in rhabdomyosarcoma interferes with normal foxo activity and the tgf-β pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373809/
https://www.ncbi.nlm.nih.gov/pubmed/25806826
http://dx.doi.org/10.1371/journal.pone.0121474
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