EWS-ETS oncoproteins: the linchpins of Ewing tumors.
Ewing tumors, which comprise Ewing's sarcoma and peripheral primitive neuroectodermal tumors, are highly aggressive and mostly affect children and adolescents. Their molecular signature is a chromosomal translocation leading to the generation of EWS-ETS (or very rarely FUS-ETS) fusion proteins that are capable of transforming cells. These oncoproteins act as aberrant transcription factors due to the fusion of an ETS DNA binding domain to a highly potent EWS (or FUS) transactivation domain. Accordingly, many EWS-ETS target genes have been identified whose dysregulation could contribute to the development of tumor formation. Furthermore, EWS-ETS oncoproteins may impact on RNA splicing or affect other proteins through disturbing their ability to form functional complexes. The molecular knowledge gained so far from studying EWS-ETS oncoproteins has not only broadened our understanding of Ewing tumors but also improved the diagnosis of these highly undifferentiated tumors. In addition, several potential prognostic markers have been uncovered and novel therapies are suggested that may improve the still dismal survival rate of Ewing tumor patients.
Janknecht
Ralf
R
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. janknecht.ralf@mayo.edu
D002885:Chromosomes, Human, Pair 16; D002891:Chromosomes, Human, Pair 21; D006801:Humans; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics / Q000502:physiology*; D034802:RNA-Binding Protein EWS / Q000235:genetics / Q000502:physiology*; D012512:Sarcoma, Ewing / Q000235:genetics / Q000503:physiopathology*; D014178:Translocation, Genetic
D050783:Proto-Oncogene Proteins c-ets; D034802:RNA-Binding Protein EWS