Which protein inhibits Tem1 to prevent premature mitotic exit?
Exit from mitosis in Saccharomyces cerevisiae is governed by the Mitotic Exit Network, a conserved Hippo-like kinase cascade initiated by small GTPase Tem1 at spindle pole bodies. Inaccurate spindle positioning would generate anucleate daughters if MEN fired prematurely. The Spindle Position Checkpoint prevents this error. Kin4 kinase, enriched at mother cell cortex and mother spindle pole body, acts as central checkpoint effector. When anaphase spindle fails to penetrate the bud neck, Kin4 phosphorylates Bfa1 subunit of the Bfa1-Bub2 GTPase activating complex. Phosphorylated Bfa1-Bub2 remains active, stimulating Tem1 GTP hydrolysis to GDP-bound inactive state and excluding Tem1 from daughter spindle pole body. This blocks downstream activation of Cdc15 kinase, Dbf2-Mob1 complex and consequent release of Cdc14 phosphatase from nucleolar Net1 sequestration. Upon correct alignment, Lte1 localized in bud antagonizes Kin4, promoting Bfa1 inactivation by polo kinase Cdc5, permitting Tem1-GTP accumulation, Cdc14 release and cyclin B degradation, thereby coupling spatial spindle position to temporal mitotic exit. Additional feedback loops involving polo-like kinases, phosphatases and SCF-mediated degradation reinforce irreversibility and protect against premature progression that would compromise genome integrity and viability.
Ref: Bardin & Amon, Molecular Cell Biology of Spindle Position Checkpoint, Nat Rev Mol Cell Biol 2001; NCBI Bookshelf, MEN and SPOC signaling.