Helene Rangone

Among the protein kinases controlling mitotic progression, the Aurora kinase family has been shown to be dysregulated in cancer. Defects in the behaviour of centrosomes are observed in tumour cells and contribute to the formation of abnormal mitotic spindles and then to aneuploidy. Roles have been established for Aurora kinases in various processes such as centrosome maturation, bipolar spindle formation as well as centromere/kinetochore attachment. Nevertheless, the direct functions of Aurora kinases in these mechanisms are not fully understood. Time lapse imaging of mitosis in Drosophila syncytial embryos carrying a maternal defective allele of Aurora A showed that when centrosomes pairs succeed in separating, 30% of the centrosomes pairs are not nucleating spindle MTs and 35 % of the pairs are nucleating spindle MTs from only one of the two centrosomes (the non nucleating centrosome then detaches in 83% of the cases). This observation, altogether with the absence of visible asters, suggest that the nucleating activity of the centrosome is compromised. To better determine the role of Aurora A at the centrosome for the establishment of the mitotic spindle we are studying partially purified centrosomal preparations from syncytial embryos. Aurora A is found in the centrosome enriched fractions and is localised to the center of asters in in vitro MT nucleation assay. Complementation assays with supernatant depleted for Aurora A shows that the kinase is required for proper nucleation of asters. We are currently studying the targets of Aurora at the centrosome and how their phosphorylation influences centrosome maturation and microtubule nucleation. Areas of interest: Mitotic kinases Centrosome Genes of interest: Aurora

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