Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone.

Ewing sarcoma EWS protein regulates midzone formation by recruiting Aurora B kinase to the midzone. Cell Cycle. 2014 Jun 19;13(15) Authors: Park H, Turkalo TK, Nelson K, Folmsbee SS, Robb C, Belford B, Azuma M Abstract Ewing sarcoma is a malignant bone cancer that primarily occurs in children and adolescents. Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene. Previously, we demonstrated that an interaction between EWS/FLI1 and wild-type EWS led to the inhibition of EWS activity and mitotic dysfunction. Although defective mitosis is considered to be a critical step in cancer initiation, it is unknown how interference with EWS contributes to Ewing sarcoma formation. Here, we demonstrate that the EWS/FLI1- and EWS-knockdown cells display a high incidence of defects in the midzone, which is a midline structure located between segregating chromatids during anaphase. Defects in the midzone can lead to the failure of cytokinesis and can result in the induction of aneuploidy. The similarity among the phenotypes of EWS/FLI1- and EWS siRNA-transfected HeLa cells points to the inhibition of EWS as the key mechanism for the induction of midzone defects. Supporting this observation, the ectopic expression of EWS rescues the high incidence of midzone defects observed in Ewing sarcoma A673 cells. We discovered that EWS interacts with Aurora B kinase, and EWS is also required for recr...
Source: Cell Cycle - Category: Cytology Authors: Tags: Cell Cycle Source Type: research