Cell Mitosis To Regulate The Kinase Aurora-a Activity Of Its Own Regulation And Mode Of Action

The Aurora serine/threonine kinases are currently one of the most intensely studied families of protein kinases, they regulate mitosis and meiosis in all eukaryotes and increasing evidence links these kinase to oncogenesis. Aurora kinases play critical roles in chromosome segregation and cell division. They are implicated in the centrosome cycle, spindle assembly, chromosome condensation, microtubule-kinetochore attachment, the spindle checkpoint and cytokinesis.Aurora kinases are regulated through phosphorylation, the binding of specific partners and ubiquitin-dependent proteolysis.Several Aurora substrates have been identified and their roles are being elucidated. The deregulation of Aurora kinases impairs spindle assembly, checkpoint function and cell division, causing missegregation of individual chromosomes or polyploidization accompanied by centrosome amplification. Aurora kinases are frequently overexpressed in cancers and the identification of Aurora A as a cancer-susceptibility gene provides a strong link between mitotic errors and carcinogenesis.All members of this kinase subfamily possess two distinct domains, a highly conserved C terminal catalytic domain and an N terminal non-catalytic extension that varies in size and sequence. The most conserved motif that can be found is located at the very beginning of the N-terminal domain, the length of this N-terminal domain varies from 7 residues to 162 residues, and seems to be responsible for the specificity of each kinase.Aurora-A plays an important role in centrosome maturation and spindle assemble. Aurora-A is localized at the spindle poles from prophase to telophase, and overexpression results in abnormal centrosome ampilification and cellular transformation in mammalian cells. The AURKA lies within a region of human chromosome 20q13 that is amplified in many forms of cancer, it encodes Aurora-A kinase consisting of 403 aa.The N terminal of Aurora-A contains Aurora boxl (3-42aa) and Aurora box2 (44-63asa), which called Aurora box.The non-catalytic domains of protein kinases fulfil at least two functions in vivo: to regulate the kinase ativity and to localize the protein.It is known that many protein kinases including tyromine kinase Src, MTK1 and ser/thr kinase such as Plk1, can be constitutively activated by eliminating their N-terminal sequences. Thus, their...