Abstract
BackgroundAurora 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.ResultAurora-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.ConclusionThese findings proved that Aurora C-T191D is not hyperactive but is constitutively active mutant.
Highlights
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 kinases are a conserved family of serine/threonine kinases that are pivotal to the successful execution of cell division
Establishment of Green fluorescence protein (GFP)-aurC stable cell lines NIH-3 T3 cells were transiently transfected with GFPaurC-WT (Wild type), GFP-aurC-CA and GFP-alone
Summary
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. Aurora kinases are a conserved family of serine/threonine kinases that are pivotal to the successful execution of cell division. 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 kinase inhibition by small molecules has been intensively studied recently as a possible cancer therapy [10,14,15,16,17,18]
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