Bfa1Bub2

Bfa1-Bub2 is a protein complex in budding yeast that functions as a GTPase-activating protein (GAP) for Tem1, a small GTP-binding protein, and thereby regulates the Mitotic Exit Network (MEN). The heterodimer consists of Bfa1 and Bub2 and plays a central role in coordinating mitotic exit with spindle position.

Localization and function: Bfa1-Bub2 localizes to spindle pole bodies and to the mother–bud neck region. As a GAP for Tem1, the complex keeps Tem1 in an inactive GDP-bound state, preventing activation of MEN when the spindle is misoriented or the daughter cell is not ready for division. This helps implement the spindle position checkpoint, ensuring that mitotic exit only proceeds under proper cellular geometry.

Regulation: The activity of Bfa1-Bub2 is regulated by multiple signals that reflect spindle orientation. Kin4 kinase maintains or strengthens Bfa1-Bub2 GAP activity in the mother cell when the spindle is misaligned. In the daughter cell, the protein Lte1 promotes Tem1 activation and thereby counteracts the Bfa1-Bub2–mediated inhibition, facilitating MEN signaling when the spindle has been correctly positioned. Phosphorylation state changes of Bfa1 (and associated regulators) dynamically modulate GAP activity during the cell cycle, integrating cues for timely mitotic exit.

Role in mitotic exit: Activation of Tem1 triggers the MEN, leading to the release and activation of the phosphatase Cdc14. Cdc14 drives cyclin-dependent kinase inactivation and orderly progression through anaphase, culminating in mitotic exit and cytokinesis.

Genetic and evolutionary context: BFA1 and Bub2 genes are essential components of the yeast spindle position checkpoint. Loss of either gene can cause premature mitotic exit or missegregation, while proper regulation ensures faithful cell division. The Bfa1-Bub2 module is a well-studied example of how spatial cues coordinate cell cycle progression in fungi.