Figure 4. Pathways controlling onset of mitotic exit and their regulation by the SCP.

The proteolysis of securin at the metaphase-to-anaphase transition liberates separase, which together with the other components of the FEAR pathway, triggers the partial release of Cdc14 from the RENT complex in early anaphase. Cdc14 activates the Cdc15 kinase (component of the MEN pathway) at the SPB, while Cdc5 inactivates Bfa1 of the Tem1 GAP complex, contributing to Tem1 activation. Moreover, the translocation of the daughter SPB into the bud brings the Tem1 GTPase in contact with Lte1, its putative exchange factor, which is also believed to lead to Tem1 activation. The PAK-like kinases Cla4 and Ste20 also contribute to full Tem1 activation by promoting the localization of Lte1 to the cortex. The result is the activation of MEN signalling and the initiation of a positive-feedback loop causing further release of Cdc14 from the nucleolus. Activation of MEN signalling and the concomitant release of Cdc14 in late anaphase is essential for activation of APC^Hct1 (APC/C activated by Hct1) and the commencement of the second phase of Clb proteolysis (the first phase of Clb proteolysis occurs as cells enter anaphase and is triggered by APC^Cdc20), leading to mitotic exit, and also cytokinesis. By triggering the degradation of FEAR proteins Spo12 and Cdc5, by dephosphorylating and promoting the GAP activity of Bfa1 and by causing induction of the Amn1 protein, Cdc14 itself turns on the switch that down-regulates MEN signalling and eventually leads to the re-sequestration of Cdc14 in the nucleolus. The main targets of regulation by the SCP are highlighted in the Figure.