Objective
Aurora protein kinases belong to the family of serine/threonine protein kinases. They are evolutionarily conserved enzymes that regulate different aspects of cell division. In vertebrates, there exists three Aurora kinases namely, Aurora A, Aurora B and Aurora C. In contrast, the C. elegans and D. melanogaster genomes encode only for two Aurora orthologues, and the S. cerevisiae genome for a single one. Aurora kinases differ in length and sequence of the amino terminal domain (non-catalytic domain), but show considerable similarity in the carboxy-terminal catalytic domain. Interestingly, even in the presence of high sequence similarity the three Aurora kinases are localized in distinct locations and perform different functions.
Aurora A is shown to play a major role in centrosome separation, centrosome maturation and in the stabilization of mitotic spindle assembly, while the Aurora B is important in the regulation of kinetochore-microtubule interactions. The function of Aurora A is conserved in human, Xenopus, Drosophila and C. elegans. Recent studies that include the crystallographic studies from the host laboratory showed the role of TPX2, an activator of human Aurora A in molecular recognition and regulation. Although the function of Aurora A is con served in human, Xenopus, Drosophila and C. elegans, there is no apparent homologue of TPX2 in their respective genomes. In a similar note, the Auroras A and B share very high sequence identity but their respective activators TPX2 and INCENP do not show a ny reasonable sequence similarity.
The proposed project aims to understand the molecular machanism involved in the activation and regulation of Aurora A from C.elegans and Drosophila and of human Aurora B mainly using X-ray crystallographic methods. Since, Aurora proteins are oncogens, the structural information derived from this study would help in designing specific inhibitors to block their activation.
Fields of science
Call for proposal
FP6-2002-MOBILITY-7
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Funding Scheme
IIF - Marie Curie actions-Incoming International FellowshipsCoordinator
BANGALORE
India