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Coordinating chromosome segregation with cell division: the molecular role of mitotic exit network proteins in the regulation of cytokinesis

Obiettivo

In all eukaryotic cells, the duplicated sister chromatids are segregated in mitosis by a series of coordinated events such as the alignment of sister chromatids in metaphase, their subsequent segregation in anaphase and division of the cell (cytokinesis). Any defect affecting the order of these events can cause chromosome mis-segregation resulting in chromosome instability, which contributes to the development of cancer through the amplification of oncogenes or the loss of tumour suppressors. It is therefore of fundamental importance to understand the molecular mechanisms that coordinate mitosis.
In budding yeast, one such mechanism is provided by a GTPase-regulated protein kinase cascade named the Mitotic Exit Network (MEN). The MEN ensures that mitotic exi t and cytokinesis become dependent on successful segregation of sister chromatids in anaphase.
The molecular mechanisms involved in control of cytokinesis by MEN proteins are still unknown. Components of the MEN are conserved among higher eukaryotes. Mamma lian homologues of yeast MEN proteins, such as Mst2, Lats, Ndr and hMOB proteins, are important regulators of cell morphogenesis, cell proliferation, apoptosis and cytokinesis. In a series of exciting papers, it has been shown that lack of their function p romote tumour formation.
These observations make the functional and systematic analysis of MEN-like pathways an important task.
We will dissect the molecular function of MEN components in cytokinesis by combining genomics, proteomics, cell biology and bioc hemistry in an interdisciplinary approach. Further to our studies in budding yeast, we will analyse MEN homologues in mammalian cells and establish their role in cell division. Thus, this proposal overlaps with the FP6 priority area regarding elucidation o f basic biological processes related to diseases, such as cancer, and will strengthen the European contribution in research activities in this area.

Campo scientifico (EuroSciVoc)

Parole chiave

Argomento(i)

Invito a presentare proposte

FP6-2005-MOBILITY-8
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Meccanismo di finanziamento

EXT - Marie Curie actions-Grants for Excellent Teams

Coordinatore

DKFZ
Contributo UE
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