%0 Journal Article
%T Aurora kinase-C-T191D is constitutively active mutant
%A Jabbar Khan
%A Sanaullah Khan
%A Sobia Attaullah
%A Ijaz Ali
%A Shahid Khan
%J BMC Cell Biology
%D 2012
%I BioMed Central
%R 10.1186/1471-2121-13-8
%X Aurora-C-T191D variant form was investigated and compared with wild type. The overexpression of Aurora-C-T191D was observed that it behaves like Aurora-C wild type (aurC-WT). Both Aurora-C-T191D and aurC-WT induce abnormal cell division resulting in centrosome amplification and multinucleation in transiently transfected cells as well as in stable cell lines. Similarly, Aurora-C-T191D and aurC-WT formed foci of colonies when grown on soft agar, indicating that a gain of Aurora-C activity is sufficient to transform cells. Furthermore, we reported that NIH-3 T3 stable cell lines overexpressing Aurora-C-T191D and its wild type partner induced tumour formation when injected into nude mice, demonstrating the oncogenic activity of enzymatically active Aurora kinase C. Interestingly enough tumour aggressiveness was positively correlated with the rate of kinase activity, making Aurora-C a potential anti-cancer therapeutic target.These findings proved that Aurora C-T191D is not hyperactive but is constitutively active mutant.Aurora kinases are a conserved family of serine/threonine kinases that are pivotal to the successful execution of cell division. Three Aurora kinases (Aurora-A, -B, and -C), which share sequence homology in their central catalytic kinase domains, have been identified in mammals [1]. All the three mammalian Aurora kinases are implicated as mitotic regulators and due to their elevated expression profiles detected in many human cancers, have generated significant interest in the cancer research field.Aurora-C is predominantly expressed in the testis [2,3] and is mainly restricted to meiotically dividing spermatocytes [4] and mouse oocytes [5]. Aurora-C is also associated with inner centromere protein (INCENP) in male spermatocytes. Moreover, it is reported that overexpressed Aurora-C kinase behaves like a dominant negative kinase for Aurora-B leading to a cytokinesis defect [6]. Aurora-C disrupts the chromosome passenger protein complexes necessary for cytok
%K Aurora-C
%K Oncogene
%K Centrosome
%K Multinucleation
%K Tumour
%U http://www.biomedcentral.com/1471-2121/13/8