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Reviews

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

¹ Department of Dermatology, ² Molecular and Environmental Toxicology Center, and ³ University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison, Wisconsin

Requests for reprints: Nihal Ahmad, Department of Dermatology, University of Wisconsin, Medical Science Center, 1300 University Avenue, Madison, WI 53706. Phone: 608-263-5359; Fax: 608-263-5223. E-mail: nahmad{at}wisc.edu

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. [Mol Cancer Ther 2007;6(7):1920–31]

Received 12/18/06; revised 5/ 4/07; accepted 5/25/07.

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