Securin與Aurora A 激酶共同調控人類大腸癌細胞的有絲分裂

Aurora A 激酶在有絲分裂中擔任重要的角色，並會大量表現在多種人類癌細胞中。Securin已被發現會調控有絲分裂並且防止染色體的不正常分離，也同樣會表現在多種人類腫瘤細胞中。然而，目前對於Aurora A與 securin 共同調控人類癌細胞的有絲分裂進行仍不清楚。在本篇論文我們發現Aurora A與securin 可共同參與調控人類大腸癌細胞的有絲分裂進行。利用免疫沉澱法，我們發現大腸癌細胞中的Aurora A蛋白會結合securin蛋白。有趣地，我們發現在securin基因缺失的大腸癌細胞中，磷酸化Aurora A與總量Aurora A的蛋白表現會大量降低。若利用GFP-securin表現載體轉殖到securin基因缺失的大腸癌細胞中，則會增加Aurora A蛋白的表現。利用轉殖Aurora A shRNA 表現載體將Aurora A的表現阻斷後，發現securin的蛋白表現也會跟著降低。相反地，利用GFP-Aurora A表現載體大量表現Aurora A時，會增加securin的蛋白表現量。當Aurora A與securin同時缺乏表現時，會造成染色體不正常的分離、有絲分裂停滯及細胞生長的抑制。此外，處理Nocodazle有絲分裂抑制劑會誘發大腸癌細胞的有絲分裂停滯，並改變Aurora A的蛋白表現與在有絲分裂期的位置。綜合以上結果，這些發現顯示Aurora A與securin可共同參與調控人類大腸癌細胞的有絲分裂進行。

關鍵字

安全蛋白

並列摘要

Aurora A kinase plays a vital role in mitosis, which is highly expressed in various human cancer cells. Securin has shown to regulate mitosis and prevents abnormal chromosomal segregation that is also highly expressed in several tumor cells. However, the co-regulation of Aurora A and securin in the mitotic progression of human cancer cells remains unclear. Here we show that Aurora A and securin can co-regulate the mitotic progression in the human colon cancer cells. Aurora A proteins could bind to securin proteins in colon cancer cells by using immunoprecipitation assays. Interestingly, the securin-null colon cancer cells markedly reduced the protein levels of phosphorylated and total Aurora A. Moreover, transfection with a GFP-securin-expressed vector increased the Aurora A protein levels. The knockdown of Aurora A by transfection with an Aurora A shRNA vector reduced the securin protein expression. In contrast, transfection of a GFP-Aurora A-expressed vector increased the securin protein levels. The loss of Aurora A and securin induced the abnormal chromosome segregation, mitotic arrest and growth inhibition. Besides, Nocodazole, a mitotic inhibitor, induced mitotic arrest and the abnormal expression and location of Aurora A proteins in colon cancer cells. Taken together, these findings demonstrate that Aurora A and securin may co-regulate the mitotic progression in human colon cancer cells.

並列關鍵字

securin ； Aurora A

參考文獻

Adams, R.R., Carmena, M., Earnshaw, W.C., 2001. Chromosomal passengers and the (aurora) ABCs of mitosis. Trends Cell Biol 11, 49-54.

Breitfeld, P.P., McKinnon, W.C., Mostov, K.E., 1990. Effect of Nocodazole on vesicular traffic to the apical and basolateral surfaces of polarized MDCK cells. J Cell Biol 111, 2365-2373.

Chao, J.I., Liu, H.F., 2006. The blockage of survivin and securin expression increases the cytochalasin B-induced cell death and growth inhibition in human cancer cells. Mol Pharmacol 69, 154-164.

Chen, J.Y., Sen, S., Amos, C.I., Wei, C.J., Jones, J.S., Lynch, P., Frazier, M.L., 2007. Association between aurora-a kinase polymorphisms and age of onset of hereditary nonpolyposis colorectal cancer in a Caucasian population. Mol Carcinog 46, 249-256.

Cormier, A., Drubin, D.G., Barnes, G., 2013. Phosphorylation regulates kinase and microtubule binding activities of the budding yeast Chromosomal Passenger Complex in vitro. J Biol Chem.

國際替代計量

Securin與Aurora A 激酶共同調控人類大腸癌細胞的有絲分裂

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