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.
Source: Mitotic Kinases and p53 Signaling. Ha GH, Breuer EK (eubreuer@lumc.edu). Biochem Res Int. 2012;2012:195903.
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Hello,
RépondreSupprimerI appreciate your idea here. p53 is a tumour suppressor protein that regulates the expression of a wide variety of genes involved in Apoptosis, Growth arrest, Inhibition of cell cycle progression. Definitely it has a good content. Thank you for imparting more of your own thoughts...
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