A model for mitotic exit in budding yeast. At the centre of the scheme is reversible phosphorylation and dephosphorylation of the Cdc14 phosphatase inhibitor Net1. At anaphase onset, separase-dependent downregulation of PP2A^Cdc55 promotes Cdk phosphorylation of Net1, amplified by Cdc5. This leads to Cdc14 early anaphase release from nucleolar inhibition by Net1 (FEAR). PP2A^Cdc55 downregulation, together with Cdc14 and spindle elongation-mediated Tem1 activation by Lte1, contribute to activation of the mitotic exit network (MEN). Kinases of the MEN cascade (e.g. Dbf2) may maintain Cdc14 release by sustaining Cdc5-amplified Net1 phosphorylation.

Comparison of budding yeast mitotic exit regulators with their counterparts in fission yeast and higher eukaryotes. The fission yeast Cdc14 orthologue Clp1 is released from the nucleolus already during mitotic entry, but remains inhibited by Cdk phosphorylation. Its activation is independent of the SIN signalling cascade, made up of the MEN orthologues, but SIN maintains Clp1 activity during completion of cytokinesis. While cytokinesis is linked to mitotic exit, as defined by re-entry into G1, both processes can be uncoupled. SIN is required for cytokinesis, but not for re-entry into the next cell cycle. The Clp1 phosphatase is not essential, raising the question as to the phosphatase(s) that reverse Cdk phosphorylation. In higher eukaryotes, Cdc14 phosphatases contribute to spindle midzone formation and cytokinesis, but are not essential at least in some organisms. Orthologues of the MEN components form part of the Hippo signalling cascade that controls transcription of cell proliferation and apoptosis genes.