Objective
The mitotic exit network (MEN) is a signaling pathway that promotes exit from mitosis in Saccharomyces cerevisiae by maintaining the protein phosphatase Cdc14 released from the nucleolus into the nucleus and the cytoplasm, where it eventually promotes mitotic cyclin degradation. MEN resembles a RAS-like signaling cascade. The GTPase Tem1 and the two component GTPase-activating protein Bfa1-Bub2, which function at the top of the MEN, have been shown to localize only to the spindle pole body (SPB, the yeast’s centrosome) that enters the daughter cell during anaphase, while they are excluded from the SPB that stays in the mother cell. Based on our observations, the differential localization of Bfa1, Bub2, and Tem1 to SPBs is determined by a different efficiency in loading of the complex onto the SPBs that is dependent on specific microtubule-cortex interactions. We have also found that polarization of the actin cytoskeleton plays an important role in the generation of the asymmetry. However, the determinants of this asymmetry and the exact mechanism are still unknown. The objectives of this proposal are to: (i) Evaluate the role played on this asymmetry by proteins that either interact with the Tem1 complex or involved in other processes of generation of polarity; (ii) Perform genetic screens to identify genes required for the asymmetric localization of Bfa1, Bub2 and Tem1; (iii) Identify the regions within Bfa1, Bub2 and Tem1 that are necessary for their localization and for the generation of the asymmetry; (iv) Examine the consequences of disrupting the asymmetry in the Tem1 complex localization on the progression through the cell cycle. Answering these questions will increase our knowledge about the regulation of the exit from mitosis and the mechanisms that control the cell cycle. Since a key function of the MEN is to maintain ploidy, and ploidy is often affected in tumors, our research will also shed light on one of the key initiation steps in tumor formation.
Fields of science
Call for proposal
FP7-PEOPLE-IRG-2008
See other projects for this call
Funding Scheme
MC-IRG - International Re-integration Grants (IRG)Coordinator
41004 Sevilla
Spain