title: Oncogenic partnerships: EWS-FLI1 protein interactions initiate key pathways of Ewing's sarcoma.
abstract: Targeted therapy for cancer, which is specifically directed toward the cancer without any potential for effects outside of controlling the tumor, is a gold standard for treatment. Ewing's sarcoma contains the potential target EWS-FLI1, as a result of a pathognomonic chromosomal translocation. The EWS-FLI1 fusion protein includes the EWS domain, a potent transcriptional activator alongside the highly conserved FLI1 ets DNA-binding domain. Because of the combination of these domains, the EWS-FLI1 fusion protein acts as an aberrant transcription factor whose expression results in cellular transformation. EWS-FLI1 functions by binding to normal cellular protein partners in transcription and splicing, similar to how a virus would corrupt normal cellular machinery for virion production. Therefore, understanding the protein-protein interactions of EWS-FLI1 and the pathways that are regulated by these partnerships will inform both oncogenesis and therapeutics. This review describes the known protein partners and transcriptional targets of EWS-FLI1, while proposing strategies for exploiting these partnerships with targeted therapy.
authors.affiliation: Department of Oncology and Pediatrics, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
authors.forename: Hayriye V
authors.initials: HV
authors.lastname: Erkizan
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Toretsky
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014178:Translocation, Genetic
chemical_list: C106031:EWS-FLI fusion protein; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D014157:Transcription Factors