Role of Ewing sarcoma proteins EWS/FLI1 and EWS in mitosis
Prof. Mizuki Azuma, Department of Molecular Biosciences
University of Kansas
Project dates: 2012-2015
Mentor: Berl Oakley
Dr. Azuma proposes to elucidate the molecular mechanism whereby the Ewing sarcoma fusion protein EWS/FLI1 leads to chromosome instability and malignant transformation. Ewing sarcoma is the second most common form of bone cancer in children and adolescents. EWS/FLI1 is a chimeric fusion protein containing EWS-derived sequences at the amino-terminal region fused to the carboxy-terminal regions of the ETS transcription factor FLI1. FLI1 is essential for hemangioblast differentiation, whereas the in vivo function of EWS is not well understood.
Dr. Azuma and her colleagues previously reported that both expression of the EWS/FLI1 fusion protein and knockdown of endogenous EWS in zebrafish embryos and in HeLa cells leads to mitotic defects. They subsequently demonstrated that EWS/FLI1 interacts with wildtype EWS, and this interaction lead to inhibition of EWS activity. Their research goal is to elucidate whether and how mitotic defects in EWS/FLI1 expressing and endogenous EWS knockdown cells lead to chromosome instability and potentially to Ewing sarcoma formation. They will address these questions by establishing and analyzing an Ewing sarcoma model in zebrafish.