文章：

极光A -极地守护者

Aurora-A — A guardian of poles

原文发布日期：2005-01-01

DOI: 10.1038/nrc1526

类型: Review Article

开放获取: 否

要点：

1. Aurora/Ipl1-related kinases are evolutionally conserved serine/threonine kinases that regulate mitotic progression in various organisms. Humans have three classes of Aurora kinases (A, B and C). Aurora-A and -B are ubiquitously expressed and regulate cell-cycle events from G2 to M phase.
2. Aurora-A is localized at centrosome during interphase, translocated to mitotic spindles in early mitotic phase and degraded after metaphase–anaphase transition. Activation of Aurora-A is required for mitotic entry, centrosome maturation, centrosome separation and chromosome alignment, and inactivation is also necessary for exit from mitosis.
3. Human Aurora-A is frequently amplified in various cancers. The levels of Aurora-A mRNA and protein are increased in those tumours and the overexpression of Aurora-A efficiently transforms immortalized rodent fibroblasts, indicating that Aurora-A is an oncoprotein.
4. Aurora-A kinase is activated by interaction with Ajuba and TPX2 during late G2 and mitotic phases, respectively.
5. Overexpression of Aurora-A induces abnormalities in G2 checkpoint and spindle checkpoint and cytokinesis failure. Those abnormalities lead to chromosome instability but are not sufficient for tumorigenesis in animal models. Additional changes such as p53 inactivation and expression of pro-survival proteins might be required for Aurora-A-mediated tumorigenesis.
6. Aurora-kinase inhibition effectively blocks cell growth and induces apoptosis in cancer cells. It might provide a new approach for the treatment of many human malignancies.

要点翻译：

1. 极光/Ipl1相关激酶是一类在进化上高度保守的丝氨酸/苏氨酸激酶，在不同生物体中调控有丝分裂进程。人类拥有三类极光激酶（A、B和C型）。极光激酶A和B广泛表达，调控从G2期到M期的细胞周期事件。
2. 极光激酶A在间期定位于中心体，在早前期转移至纺锤体，并在中期-后期转换后降解。极光激酶A的激活是细胞进入有丝分裂、中心体成熟、中心体分离和染色体排列所必需的，而其失活也是退出有丝分裂的必要条件。
3. 人类极光激酶A在多种癌症中频繁扩增。这些肿瘤中极光激酶A的mRNA和蛋白水平均升高，且其过表达能有效转化永生化啮齿动物成纤维细胞，表明极光激酶A是一种癌蛋白。
4. 极光激酶A分别通过晚期G2期和M期与Ajuba及TPX2的相互作用被激活。
5. 极光激酶A的过表达会诱导G2检查点和纺锤体检查点异常以及胞质分裂失败。这些异常会导致染色体不稳定性，但在动物模型中不足以引发肿瘤发生。极光激酶A介导的肿瘤发生可能还需要其他变化，如p53失活和促存活蛋白的表达。
6. 极光激酶抑制剂能有效阻断癌细胞生长并诱导其凋亡，这可能为治疗多种人类恶性肿瘤提供新途径。

英文摘要：

The three human homologues of Aurora kinases (A, B and C) are essential for proper execution of various mitotic events and are important for maintaining genomic integrity. Aurora-A is mainly localized at spindle poles and the mitotic spindle during mitosis, where it regulates the functions of centrosomes, spindles and kinetochores required for proper mitotic progression. Recent studies have revealed that Aurora-A is frequently overexpressed in various cancer cells, indicating its involvement in tumorigenesis. What are the normal physiological roles of Aurora-A, how are these regulated and how might the enzyme function during tumorigenesis?

摘要翻译： 

人类三种Aurora激酶同源物（A、B和C）对于多种有丝分裂事件的正确执行至关重要，并在维持基因组完整性方面发挥重要作用。Aurora-A主要定位于有丝分裂期的纺锤极和纺锤体，在此调控中心体、纺锤体和动粒的功能，以确保有丝分裂的正常进行。近期研究发现，Aurora-A在多种癌细胞中频繁过表达，提示其参与肿瘤发生。Aurora-A的正常生理功能是什么？这些功能如何被调控？在肿瘤发生过程中该酶可能发挥怎样的作用？

原文链接：

Aurora-A — A guardian of poles