Role of the protein kinase Mastl in Cell Division .. (Mastl CDC)
Role of the protein kinase Mastl in Cell Division and Cancer
Start date: Sep 1, 2012,
End date: Aug 31, 2014
The cell division cycle is an essential step in living organisms. Different studies have led to a model where cell cycle kinases act as major engines to promote cell cycle progression throughout the different phases of the cell cycle. In addition to Cyclin- dependent kinases (Cdks), Polo-like and Aurora kinases, other kinases have recently emerged as important regulators of cell cycle progression. Among them, a new kinase known as Mastl in mammals, and Greatwall in Xenopus and Drosophila, has been shown to be important for mitosis. The decision to enter mitosis and the maintenance of the mitotic state depends on phosphorylations by Cyclin B/Cdk1 complexes, which can be counteracted by the phosphatase PP2A. Recent studies have pointed to Mastl/Greatwall as a critical regulator of PP2A in this context.The aim of this project is to characterize the function of Mastl in the cell cycle in mammalian cells, and to evaluate its potential as target for cancer therapy. Three complementary lines of investigation will be used to address this issue:1. Analysis of Mastl function in vivo in a Mastl knock-out mouse, and in different cellular systems derived from that model, such as embryonic fibroblasts and induced pluripotent stem cells (iPSs).2. Identification of Mastl interactors and substrates through the combination of chemical genetics and proteomic methods.3. Validation of Mastl as a target for antitumoral therapy by inhibition of Mastl, alone or in combination with other therapies, in human tumor cell lines and in cancer mouse models.
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