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Biochem Res Int. 2012; 2012: 195903.
Published online Jul 19, 2012. doi:  10.1155/2012/195903
PMCID: PMC3407609
Mitotic Kinases and p53 Signaling
Geun-Hyoung Ha 1 and Eun-Kyoung Yim Breuer 1 , 2 *
1Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
2Department of Molecular Pharmacology and Therapeutics, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
*Eun-Kyoung Yim Breuer: eubreuer/at/lumc.edu
Academic Editor: Mandi M. Murph
Received April 6, 2012; Accepted May 18, 2012.
Abstract
Mitosis is tightly regulated and any errors in this process often lead to aneuploidy, genomic instability, and tumorigenesis. Deregulation of mitotic kinases is significantly associated with improper cell division and aneuploidy. Because of their importance during mitosis and the relevance to cancer, mitotic kinase signaling has been extensively studied over the past few decades and, as a result, several mitotic kinase inhibitors have been developed. Despite promising preclinical results, targeting mitotic kinases for cancer therapy faces numerous challenges, including safety and patient selection issues. Therefore, there is an urgent need to better understand the molecular mechanisms underlying mitotic kinase signaling and its interactive network. Increasing evidence suggests that tumor suppressor p53 functions at the center of the mitotic kinase signaling network. In response to mitotic spindle damage, multiple mitotic kinases phosphorylate p53 to either activate or deactivate p53-mediated signaling. p53 can also regulate the expression and function of mitotic kinases, suggesting the existence of a network of mutual regulation, which can be positive or negative, between mitotic kinases and p53 signaling. Therefore, deciphering this regulatory network will provide knowledge to overcome current limitations of targeting mitotic kinases and further improve the results of targeted therapy.
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