Aurora kinase-C-T191D is constitutively active mutant
1 Department of Biological Sciences, Gomal University Dera Ismail Khan, Dera Ismail Khan, Pakistan
2 Institute of Genetics and Development, University of Rennes1, Rennes1, France
3 Department of Zoology, Kohat University of Science and Technology, Kohat, Pakistan
4 Department of Zoology, Islamia College Peshawar (A Public Sector University), University Campus, Jamrod Road, Peshawar 25120 Khyber Pakhtunkhwa, Pakistan
5 Institute of Biotechnology and Genetic Engineering, Khyber Pakhtunkhwa University of agriculture Peshawar, Khyber Pakhtunkhwa, Pakistan
BMC Cell Biology 2012, 13:8 doi:10.1186/1471-2121-13-8Published: 26 March 2012
Aurora kinases (Aurora-A, B and C) belong to a family of conserved serine/threonine kinases which are key regulators of cell cycle progression. Aurora-A and Aurora-B are expressed in somatic cells and involved in cell cycle regulation while aurora-C is meiotic chromosome passenger protein. As Aurora kinase C is rarely expressed in normal somatic cells and has been found over expressed in many cancer lines. It is suggested that Aurora-C-T191D is not hyperactive mutant.
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.