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通过有丝分裂激酶调控有丝分裂:癌症治疗的新机遇。

Regulation of mitosis via mitotic kinases: new opportunities for cancer management.

作者信息

Schmit Travis L, Ahmad Nihal

机构信息

Department of Dermatology, University of Wisconsin, Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA.

出版信息

Mol Cancer Ther. 2007 Jul;6(7):1920-31. doi: 10.1158/1535-7163.MCT-06-0781.

Abstract

Mitosis, a critical and highly orchestrated event in the cell cycle, decides how cells divide and transmit genetic information from one cell generation to the next. Errors in the choreography of these events may lead to uncontrolled proliferation, aneuploidy, and genetic instability culminating in cancer development. Considering the central role of phosphorylation in mitotic checkpoints, spindle function, and chromosome segregation, it is not surprising that several mitotic kinases have been implicated in tumorigenesis. These kinases play pivotal roles throughout cellular division. From DNA damage and spindle assembly checkpoints before entering mitosis, to kinetochore and centrosome maturation and separation, to regulating the timing of entrance and exit of mitosis, mitotic kinases are essential for cellular integrity. Therefore, targeting the mitotic kinases that control the fidelity of chromosome transmission seems to be a promising avenue in the management of cancer. This review provides an insight into the mechanism of mitotic signaling, especially the role of critical mitotic kinases. We have also discussed the possibilities of the use of mitotic kinases in crafting novel strategies in cancer management.

摘要

有丝分裂是细胞周期中一个关键且高度协调的事件,它决定了细胞如何分裂以及如何将遗传信息从一个细胞世代传递到下一个细胞世代。这些事件编排过程中的错误可能会导致细胞不受控制地增殖、非整倍体形成以及遗传不稳定,最终引发癌症。鉴于磷酸化在有丝分裂检查点、纺锤体功能和染色体分离中发挥的核心作用,有几种有丝分裂激酶与肿瘤发生有关也就不足为奇了。这些激酶在整个细胞分裂过程中都起着关键作用。从进入有丝分裂之前的DNA损伤和纺锤体组装检查点,到动粒和中心体的成熟与分离,再到调节有丝分裂的进入和退出时间,有丝分裂激酶对于细胞完整性至关重要。因此,靶向控制染色体传递保真度的有丝分裂激酶似乎是癌症治疗中一条很有前景的途径。本综述深入探讨了有丝分裂信号传导的机制,尤其是关键有丝分裂激酶的作用。我们还讨论了在制定癌症治疗新策略中使用有丝分裂激酶的可能性。

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