Functional significance of Aurora kinase A in centrosome amplification and genomic instability.

摘要

Aurora kinase (Aur) A is the member of a Serine/Threonine protein kinase family that is represented by a single prototypic Ip11 kinase in yeast and additional paralogues in metazoan organisms. Among mammals, this kinase family consists of three members, AurA, AurB, and AurC while in Drosophila, C. elegans and Xenopus, two members, AurA and B have been identified. Since its discovery about a decade ago, Aur family of kinases has received significant attention because of frequent over expression of all three kinases detected in human cancers and their roles as critical regulators of mitotic cell proliferation and chromosome segregation processes. Ectopic elevated expression of AurA in mammalian cells in vitro was reported to induce oncogenic transformation in cells along with centrosome amplification and chromosomal instability. Chromosomal ploidy alterations correlating with AurA over expression has since been detected in several human cancers, rat, and mouse in vivo mammary cancer model systems. These findings suggest that chromosomal instability is a genetically determined mutant phenotype induced due to anomalies in the molecular pathways critical to the development of malignant transformation in cells