正確的染色體分離對於細胞分裂，維持基因的穩定性是非常重要的。正確的kinetochore-microtubule 連結，在染色體分離過程中扮演了關鍵性的角色。Aurora-B為極光激酶家族成員之一，屬於 chromosomal passenger proteins (CPCs)的一種，當細胞分裂時，若發生不正當的kinetochore-microtubule 連結，負責執行紡錘絲校正點(spindle assembly checkpoint – SAC)之功能，以確保染色體分離過程正確。Aurora-C為另一個極光激酶家族成員，主要表現於男性生殖細胞中，它在細胞中的位置與Aurora-B類似，因此亦被認為是CPCs。最近有研究顯示，在許多人類癌細胞株及癌組織檢體中，偵測到Aurora-C不正常的大量表現，然而目前對於在癌細胞中，Aurora-C大量表現之生理功能尚不清楚。本論文中，我們發現CPCs會因為不正常表現的Aurora-C而無法位於其正確的位置，且其表現量會因隨著Aurora-C表現量的上升而明顯下降，此時Aurora-B激酶的活性也會受到抑制。我們發現，Aurora-B的受質－ Histone H3 Ser10和MCAK，在大量表現Aurora-C的細胞中，其磷酸化程度是明顯降低的。免疫螢光染色進一步發現，當細胞需要啟動功能性SAC時，Aurora-C的大量表現會造成BubR1不會出現在kinetochore的位置，表示細胞啟動功能性SAC的能力降低。有趣的是， Aurora-C影響CPCs、Aurora-B激酶活性以及SAC的功能，是與其激酶活性無關的。此外，利用免疫沈澱反應，我們發現Aurora-C會影響細胞內原本存在的Aurora-B與INCENP之間的交互作用。綜合以上實驗結果，我們推測，在體細胞中不正常大量表現的Aurora-C，會造成Aurora-B無法執行其功能，導致染色體不穩定性，進一步使得細胞走向癌化。

Accurate segregation of chromosomes during mitosis is important for genetic stability maintenance, and the exact kinetochore-microtubule attachment plays a pivotal role in this process. The Aurora kinase family member – Aurora-B, which is a chromosomal passenger protein, serves as a mitotic spindle checkpoint protein that is necessary for proper chromosomal segregation. Aurora-C, another member of the Aurora kinase family, is dominantly expressed in male germ cells. According to the previous reports, the subcellular localization of Aurora-C is similar to Aurora-B, implying that Aurora-C may serve as a chromosomal passenger protein. Several studies indicated that the expression of Aurora-C can be detected in many somatic cancer cell lines and human cancers. However, the biological function of Aurora-C overexpression in cancers remains uncertain. In this study, exogenic expressed Aurora-C-GFP can result in the displacement of kinetochore- decorated chromosomal passenger proteins (CPCs), and decreased the expression of the CPCs in a dose-dependent manner. On the other hands, the phosphorylation levels of Aurora-B substrates – Histone H3 and MCAK were decreased by overexpressed Aurora-C indicating that the kinase activity of Aurora-B was abolished by Aurora-C. Moreover, activation of spindle checkpoint protein - BubR1, was also impaired in the cells with exogenic expressed Aurora-C-GFP. Those phenomena are resulted from the disrupted interaction between Aurora-B and INCENP by Aurora-C-GFP in a kinase-independent manner. Taken together, our results suggest that aberrantly expressed Aurora-C in somatic cells can abolish the spindle checkpoint function of Aurora-B, which is helpful chromosomal instability and lead to tumorigenesis.

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