EWS-FLI1 fusion protein (EWS-FLI1)

The **EWS-FLI1 fusion protein** is an aberrant transcription factor resulting from a chromosomal translocation t(11;22)(q24;q12) that fuses the EWS gene (EWSR1) with the FLI1 gene, leading to the expression of a chimeric protein specific for Ewing sarcoma and related tumors[5][2]. This fusion protein combines the N-terminal transactivation domain of EWS with the C-terminal DNA-binding domain of FLI1, creating an oncogenic mechanism that both activates and represses transcription of target genes as well as modulating alternative RNA splicing[3][6]. The **EWS-FLI1 fusion transcript** is considered a molecular hallmark and driver of Ewing sarcoma, functioning as the primary pathogenic lesion and a key diagnostic biomarker[5]. Drug discovery has focused on inhibiting EWS-FLI1's protein-protein interactions, inhibiting cofactors (such as LSD1, BRD4), or promoting its degradation, with compounds like YK-4-279 under investigation[3][2]. The transcript and its encoded protein are central to disease biology, affecting chromatin structure, transcriptional programs, and splicing networks that drive tumorigenesis[2][6]. Detection of the EWS-FLI1 fusion transcript is essential for the diagnosis and management of Ewing sarcoma patients.

Other names

EWS/FLI1 fusion transcriptEWS::FLI1EWS-FLI-1EWSR1-FLI1

Inhibition of EWS-FLI1 protein-protein interactions, Disruption of EWS-FLI1-mediated transcription and splicing, Promotion of proteasomal degradation