The PAX3-FOXO1 fusion protein present in rhabdomyosarcoma interferes with normal FOXO activity and the TGF-? 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-? response. PAX3-FOXO1 may contribute to tumor formation by inhibiting the tumor suppressor activities which are characteristic of both FOXO family members and TGF-? pathways. The recognition of this mechanism raises new questions about how FOXO family members function.

SUBMITTER: Schmitt-Ney M 

PROVIDER: S-EPMC4373809 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature