Phase separation of the oncogenic fusion protein EWS::FLI1 is modulated by its DNA-binding domain.

ABSTRACT: Ewing sarcoma (EwS) is an aggressive cancer of bone and soft tissue that predominantly affects children and young adults. A chromosomal translocation joins the low-complexity domain (LCD) of the RNA-binding protein EWS (EWS^LCD) with the DNA-binding domain of Friend leukemia integration 1 (FLI1^DBD), creating EWS::FLI1, a potent fusion oncoprotein essential for EwS development and responsible for over 85% of EwS tumors. EWS::FLI1 forms biomolecular condensates in vivo and promotes tumorigenesis through mediation of aberrant transcriptional changes and by interfering with the normal functions of nucleic acid-binding proteins like EWS through a dominant-negative mechanism. In particular, the expression of EWS::FLI1 in EwS directly interferes with the biological functions

SUBMITTER: Selig EE 

PROVIDER: S-EPMC12107149 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature