近來,，來自愛丁堡大學(xué)的研究人員在PLoS Biology雜志上發(fā)表文章稱：他們?cè)诩?xì)胞分裂上有了新的認(rèn)識(shí)，明確了調(diào)控細(xì)胞分裂的兩個(gè)關(guān)鍵蛋白的作用方式,。

當(dāng)正常細(xì)胞增殖失去控制的時(shí)候,，過度增殖會(huì)引發(fā)細(xì)胞癌變導(dǎo)致腫瘤的發(fā)生，這項(xiàng)研究可能對(duì)開發(fā)抑制腫瘤細(xì)胞增殖發(fā)揮抗腫瘤的藥物意義非常大,。

研究人員將這種能抑制腫瘤細(xì)胞增殖的潛在開發(fā)藥物稱為“有絲分裂拮抗藥”,，這些拮抗藥將有可能改善癌癥患者接受化療后帶來的相關(guān)副作用如化療會(huì)損傷正常神經(jīng)細(xì)胞。這類拮抗藥物的研發(fā)可以幫助優(yōu)化癌癥病人的個(gè)性化化療,。

為了搞清楚參與細(xì)胞分裂過程的各種蛋白質(zhì)在細(xì)胞內(nèi)如何相互作用,，研究人員運(yùn)用高分辨率顯微鏡觀察了細(xì)胞的三維形態(tài)，確定了參與調(diào)控細(xì)胞分裂的各種蛋白質(zhì)的具體位置,，同時(shí)也確定了調(diào)控細(xì)胞增殖的一個(gè)關(guān)鍵的蛋白質(zhì)如何結(jié)合并激活分裂過程中兩個(gè)關(guān)鍵酶,。早期研究已證明了這兩個(gè)酶是研發(fā)抗腫瘤藥物的靶點(diǎn)，最新的發(fā)現(xiàn)使得科學(xué)家明確了如何制造更好的藥物來阻止兩種酶的活性,。

該研究主要領(lǐng)導(dǎo)人--愛丁堡大學(xué)生物科學(xué)學(xué)院Mar Carmena教授稱：正常細(xì)胞的分裂過程是一個(gè)復(fù)雜并嚴(yán)格受控制的過程,，一旦這一平衡被打破的話，細(xì)胞增殖將失控導(dǎo)致癌癥的發(fā)生,。我們只有對(duì)調(diào)控細(xì)胞增殖的蛋白質(zhì)有了充分的了解,，才能設(shè)計(jì)出更有效的癌癥治療措施。(生物谷 Bioon.com)

doi:10.1371/journal.pbio.1001250
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The Chromosomal Passenger Complex Activates Polo Kinase at Centromeres

Mar Carmena1*, Xavier Pinson2, Melpi Platani1, Zeina Salloum2, Zhenjie Xu1, Anthony Clark1, Fiona MacIsaac1,et al.

The coordinated activities at centromeres of two key cell cycle kinases, Polo and Aurora B, are critical for ensuring that the two sister kinetochores of each chromosome are attached to microtubules from opposite spindle poles prior to chromosome segregation at anaphase. Initial attachments of chromosomes to the spindle involve random interactions between kinetochores and dynamic microtubules, and errors occur frequently during early stages of the process. The balance between microtubule binding and error correction (e.g., release of bound microtubules) requires the activities of Polo and Aurora B kinases, with Polo promoting stable attachments and Aurora B promoting detachment. Our study concerns the coordination of the activities of these two kinases in vivo. We show that INCENP, a key scaffolding subunit of the chromosomal passenger complex (CPC), which consists of Aurora B kinase, INCENP, Survivin, and Borealin/Dasra B, also interacts with Polo kinase in Drosophila cells. It was known that Aurora A/Bora activates Polo at centrosomes during late G2. However, the kinase that activates Polo on chromosomes for its critical functions at kinetochores was not known. We show here that Aurora B kinase phosphorylates Polo on its activation loop at the centromere in early mitosis. This phosphorylation requires both INCENP and Aurora B activity (but not Aurora A activity) and is critical for Polo function at kinetochores. Our results demonstrate clearly that Polo kinase is regulated differently at centrosomes and centromeres and suggest that INCENP acts as a platform for kinase crosstalk at the centromere. This crosstalk may enable Polo and Aurora B to achieve a balance wherein microtubule mis-attachments are corrected, but proper attachments are stabilized allowing proper chromosome segregation.